Type 2 Diabetes

The history and findings in this case are suggestive of chronic kidney disease (CKD).

CKD affects between 8% and 16% of the population worldwide. Risk factors for CKD are numerous and include T2D, hypertension, and prediabetes. Diabetes is the leading cause of CKD. Up to 40% of patients with diabetes develop diabetic kidney disease, which can progress to end-stage renal disease (ESRD) requiring dialysis or kidney transplantation. In fact, diabetic kidney disease is the top cause of ESRD in the United States.

Diagnostic criteria for CKD include elevated urinary albumin excretion (albuminuria) and/or eGFR < 60 mL/1.73 m² that persists for more than 3 months. The normal presentation of diabetic kidney disease includes long-standing diabetes, retinopathy, albuminuria without gross hematuria, and gradually progressive decline of eGFR. However, signs of diabetic kidney disease may be present in patients at diagnosis or without retinopathy in T2D. Reduced eGFR without albuminuria has been frequently reported in both type 1 diabetes (T1D) and T2D and is becoming increasingly common as the prevalence of diabetes rises in the United States.

Chronic kidney disease is usually identified through routine screening with serum chemistry profile and urine studies or as an incidental finding. Less often, patients may present with symptoms, such as gross hematuria, "foamy urine" (a sign of albuminuria), nocturia, flank pain, or decreased urine output. In advanced cases, patients may report fatigue, poor appetite, nausea, vomiting, a metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnea, and/or peripheral edema.

The American Diabetes Association (ADA) 2023 Standards of Care in Diabetes describes five stages of CKD. Stages 1-2 are defined by evidence of high albuminuria with eGFR ≥ 60 mL/min/1.73 m², while stages 3-5 are defined by progressively lower ranges of eGFR. Of note, at any eGFR, the degree of albuminuria is associated with risk for cardiovascular disease, CKD progression, and mortality. Thus, as noted by the ADA Standards, both eGFR and albuminuria should be used to guide treatment decisions; additionally, eGFR levels are essential for modifying drug dosages or restrictions of use, and the degree of albuminuria should influence selection of antihypertensive agents and glucose-lowering medications.

According to the ADA 2023 Standards of Care in Diabetes, for people with non–dialysis-dependent CKD, dietary protein intake should be ∼0.8 g/kg body weight per day (the recommended daily allowance), as this level has been shown to slow GFR decline compared with higher levels of dietary protein intake, with evidence of a greater effect over time. Conversely, higher levels of dietary protein intake (> 20% of daily calories from protein or > 1.3 g/kg/d) have been associated with increased albuminuria, more rapid kidney function loss, and cardiovascular disease mortality. For patients on dialysis, higher levels of dietary protein intake should be considered, because malnutrition is a significant problem in some of these patients.

Urinary excretion of sodium and potassium may be impaired in patients with reduced eGFR. Thus, restriction of dietary sodium to < 2300 mg/d may help to control blood pressure and reduce cardiovascular risk, and restriction of dietary potassium may be necessary to control serum potassium concentration. 

Intensive glycemic control with the goal of achieving near-normoglycemia has been shown to delay the onset and progression of albuminuria and reduced eGFR in patients with diabetes. Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of T1D while a variety of agents were used in clinical trials of T2D, supporting the conclusion that glycemic control itself helps prevent CKD and its progression. However, the presence of CKD affects the risks and benefits of intensive glycemic control and several glucose-lowering medications. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial of T2D, increased adverse effects of intensive glycemic control (hypoglycemia and mortality) were seen among patients with kidney disease at baseline. Moreover, it may take at least 2 years to see improved eGFR outcomes as an effect of intensive glycemic control. Therefore, in some patients with prevalent CKD and substantial comorbidity, target A1c levels may be less intensive.

According to guidance from the US Food and Drug Administration, eGFR should be monitored while taking metformin and metformin is contraindicated in patients with an eGFR < 30 mL/min/1.73 m². Clinicians should assess the benefits and risks of continuing treatment when eGFR falls to < 45 mL/min/1.73 m². 

The ADA recommends that sodium–glucose cotransporter 2 inhibitors be given to all patients with stage 3 CKD or higher and T2D, regardless of glycemic control, as they have been shown to delay CKD progression and reduce heart failure risk independent of glycemic control. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) also have direct effects on the kidney and have been reported to improve renal outcomes compared with placebo. In patients for whom cardiovascular risk is a predominant problem, the ADA suggests using GLP-1 RAs for cardiovascular risk reduction.

Comprehensive guidance on the management of CKD in patients with T2D is available in the ADA 2023 Standards of Care in Diabetes.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of chronic kidney disease (CKD).

CKD affects between 8% and 16% of the population worldwide. Risk factors for CKD are numerous and include T2D, hypertension, and prediabetes. Diabetes is the leading cause of CKD. Up to 40% of patients with diabetes develop diabetic kidney disease, which can progress to end-stage renal disease (ESRD) requiring dialysis or kidney transplantation. In fact, diabetic kidney disease is the top cause of ESRD in the United States.

Diagnostic criteria for CKD include elevated urinary albumin excretion (albuminuria) and/or eGFR < 60 mL/1.73 m² that persists for more than 3 months. The normal presentation of diabetic kidney disease includes long-standing diabetes, retinopathy, albuminuria without gross hematuria, and gradually progressive decline of eGFR. However, signs of diabetic kidney disease may be present in patients at diagnosis or without retinopathy in T2D. Reduced eGFR without albuminuria has been frequently reported in both type 1 diabetes (T1D) and T2D and is becoming increasingly common as the prevalence of diabetes rises in the United States.

Chronic kidney disease is usually identified through routine screening with serum chemistry profile and urine studies or as an incidental finding. Less often, patients may present with symptoms, such as gross hematuria, "foamy urine" (a sign of albuminuria), nocturia, flank pain, or decreased urine output. In advanced cases, patients may report fatigue, poor appetite, nausea, vomiting, a metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnea, and/or peripheral edema.

The American Diabetes Association (ADA) 2023 Standards of Care in Diabetes describes five stages of CKD. Stages 1-2 are defined by evidence of high albuminuria with eGFR ≥ 60 mL/min/1.73 m², while stages 3-5 are defined by progressively lower ranges of eGFR. Of note, at any eGFR, the degree of albuminuria is associated with risk for cardiovascular disease, CKD progression, and mortality. Thus, as noted by the ADA Standards, both eGFR and albuminuria should be used to guide treatment decisions; additionally, eGFR levels are essential for modifying drug dosages or restrictions of use, and the degree of albuminuria should influence selection of antihypertensive agents and glucose-lowering medications.

According to the ADA 2023 Standards of Care in Diabetes, for people with non–dialysis-dependent CKD, dietary protein intake should be ∼0.8 g/kg body weight per day (the recommended daily allowance), as this level has been shown to slow GFR decline compared with higher levels of dietary protein intake, with evidence of a greater effect over time. Conversely, higher levels of dietary protein intake (> 20% of daily calories from protein or > 1.3 g/kg/d) have been associated with increased albuminuria, more rapid kidney function loss, and cardiovascular disease mortality. For patients on dialysis, higher levels of dietary protein intake should be considered, because malnutrition is a significant problem in some of these patients.

Urinary excretion of sodium and potassium may be impaired in patients with reduced eGFR. Thus, restriction of dietary sodium to < 2300 mg/d may help to control blood pressure and reduce cardiovascular risk, and restriction of dietary potassium may be necessary to control serum potassium concentration. 

Intensive glycemic control with the goal of achieving near-normoglycemia has been shown to delay the onset and progression of albuminuria and reduced eGFR in patients with diabetes. Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of T1D while a variety of agents were used in clinical trials of T2D, supporting the conclusion that glycemic control itself helps prevent CKD and its progression. However, the presence of CKD affects the risks and benefits of intensive glycemic control and several glucose-lowering medications. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial of T2D, increased adverse effects of intensive glycemic control (hypoglycemia and mortality) were seen among patients with kidney disease at baseline. Moreover, it may take at least 2 years to see improved eGFR outcomes as an effect of intensive glycemic control. Therefore, in some patients with prevalent CKD and substantial comorbidity, target A1c levels may be less intensive.

According to guidance from the US Food and Drug Administration, eGFR should be monitored while taking metformin and metformin is contraindicated in patients with an eGFR < 30 mL/min/1.73 m². Clinicians should assess the benefits and risks of continuing treatment when eGFR falls to < 45 mL/min/1.73 m². 

The ADA recommends that sodium–glucose cotransporter 2 inhibitors be given to all patients with stage 3 CKD or higher and T2D, regardless of glycemic control, as they have been shown to delay CKD progression and reduce heart failure risk independent of glycemic control. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) also have direct effects on the kidney and have been reported to improve renal outcomes compared with placebo. In patients for whom cardiovascular risk is a predominant problem, the ADA suggests using GLP-1 RAs for cardiovascular risk reduction.

Comprehensive guidance on the management of CKD in patients with T2D is available in the ADA 2023 Standards of Care in Diabetes.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of chronic kidney disease (CKD).

CKD affects between 8% and 16% of the population worldwide. Risk factors for CKD are numerous and include T2D, hypertension, and prediabetes. Diabetes is the leading cause of CKD. Up to 40% of patients with diabetes develop diabetic kidney disease, which can progress to end-stage renal disease (ESRD) requiring dialysis or kidney transplantation. In fact, diabetic kidney disease is the top cause of ESRD in the United States.

Diagnostic criteria for CKD include elevated urinary albumin excretion (albuminuria) and/or eGFR < 60 mL/1.73 m² that persists for more than 3 months. The normal presentation of diabetic kidney disease includes long-standing diabetes, retinopathy, albuminuria without gross hematuria, and gradually progressive decline of eGFR. However, signs of diabetic kidney disease may be present in patients at diagnosis or without retinopathy in T2D. Reduced eGFR without albuminuria has been frequently reported in both type 1 diabetes (T1D) and T2D and is becoming increasingly common as the prevalence of diabetes rises in the United States.

Chronic kidney disease is usually identified through routine screening with serum chemistry profile and urine studies or as an incidental finding. Less often, patients may present with symptoms, such as gross hematuria, "foamy urine" (a sign of albuminuria), nocturia, flank pain, or decreased urine output. In advanced cases, patients may report fatigue, poor appetite, nausea, vomiting, a metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnea, and/or peripheral edema.

The American Diabetes Association (ADA) 2023 Standards of Care in Diabetes describes five stages of CKD. Stages 1-2 are defined by evidence of high albuminuria with eGFR ≥ 60 mL/min/1.73 m², while stages 3-5 are defined by progressively lower ranges of eGFR. Of note, at any eGFR, the degree of albuminuria is associated with risk for cardiovascular disease, CKD progression, and mortality. Thus, as noted by the ADA Standards, both eGFR and albuminuria should be used to guide treatment decisions; additionally, eGFR levels are essential for modifying drug dosages or restrictions of use, and the degree of albuminuria should influence selection of antihypertensive agents and glucose-lowering medications.

According to the ADA 2023 Standards of Care in Diabetes, for people with non–dialysis-dependent CKD, dietary protein intake should be ∼0.8 g/kg body weight per day (the recommended daily allowance), as this level has been shown to slow GFR decline compared with higher levels of dietary protein intake, with evidence of a greater effect over time. Conversely, higher levels of dietary protein intake (> 20% of daily calories from protein or > 1.3 g/kg/d) have been associated with increased albuminuria, more rapid kidney function loss, and cardiovascular disease mortality. For patients on dialysis, higher levels of dietary protein intake should be considered, because malnutrition is a significant problem in some of these patients.

Urinary excretion of sodium and potassium may be impaired in patients with reduced eGFR. Thus, restriction of dietary sodium to < 2300 mg/d may help to control blood pressure and reduce cardiovascular risk, and restriction of dietary potassium may be necessary to control serum potassium concentration. 

Intensive glycemic control with the goal of achieving near-normoglycemia has been shown to delay the onset and progression of albuminuria and reduced eGFR in patients with diabetes. Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of T1D while a variety of agents were used in clinical trials of T2D, supporting the conclusion that glycemic control itself helps prevent CKD and its progression. However, the presence of CKD affects the risks and benefits of intensive glycemic control and several glucose-lowering medications. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial of T2D, increased adverse effects of intensive glycemic control (hypoglycemia and mortality) were seen among patients with kidney disease at baseline. Moreover, it may take at least 2 years to see improved eGFR outcomes as an effect of intensive glycemic control. Therefore, in some patients with prevalent CKD and substantial comorbidity, target A1c levels may be less intensive.

According to guidance from the US Food and Drug Administration, eGFR should be monitored while taking metformin and metformin is contraindicated in patients with an eGFR < 30 mL/min/1.73 m². Clinicians should assess the benefits and risks of continuing treatment when eGFR falls to < 45 mL/min/1.73 m². 

The ADA recommends that sodium–glucose cotransporter 2 inhibitors be given to all patients with stage 3 CKD or higher and T2D, regardless of glycemic control, as they have been shown to delay CKD progression and reduce heart failure risk independent of glycemic control. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) also have direct effects on the kidney and have been reported to improve renal outcomes compared with placebo. In patients for whom cardiovascular risk is a predominant problem, the ADA suggests using GLP-1 RAs for cardiovascular risk reduction.

Comprehensive guidance on the management of CKD in patients with T2D is available in the ADA 2023 Standards of Care in Diabetes.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical findings are consistent with a diagnosis of claw toe, which can be caused by diabetes-related peripheral neuropathy.

According to the International Diabetes Federation, diabetes currently affects approximately 537 million adults worldwide. The number of individuals living with diabetes is expected to exceed 640 million by 2030 and 780 million by 2045. In the United States, more than 37 million people are living with diabetes.

Foot complications related to diabetes represent a significant economic and social burden and can profoundly affect a patient's quality of life and medical outcomes. Common diabetes-related foot complications include foot deformity and peripheral neuropathy, both of which increase the risk for ulceration and amputation. The most common deformity is at the metatarsophalangeal joint (MTPJ). As many as 85% of patients with a history of ulcers and amputation have an MTPJ deformity such as claw toe or hammertoe.

Although they are often grouped together, claw toe and hammertoe have distinct features. Extended MTPJ, flexed proximal interphalangeal joint (PIPJ), and flexed distal interphalangeal joint (DIPJ) are characteristic of claw toe. While hammertoe also has extended MTPJ and flexed PIPJ, the DIPJ is extended rather than flexed. In both cases, the area of high pressure at risk for skin breakdown and ulceration is at the metatarsal head as a result of MTPJ hyperextension deformity. 

Prompt detection and care of diabetes-related foot complications can minimize progression and negative consequences on patients' health and quality of life. According to the American Diabetes Association, all patients with diabetes should undergo a comprehensive foot evaluation at least annually to identify risk factors for ulceration and amputation, which include foot deformities, poor glycemic control, peripheral neuropathy, cigarette smoking, preulcerative callus or corn, peripheral artery disease, chronic kidney disease, visual impairment, and a history of ulceration or amputation. When patients present with a history of ulceration or amputation, a foot inspection should be conducted at each visit. 

A comprehensive foot evaluation should include inspection of the skin, evaluation of any foot deformities, a neurologic assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature, vibration), and a vascular assessment, including pulses in the legs and feet.

Patients should be educated on risk factors and appropriate management of foot-related complications, including the importance of effective glycemic control and daily monitoring of feet. Treatment may be medical, surgical, or both, as indicated by the individual patient's presentation. Conservative treatment approaches include footwear that is extra wide or deep, avoiding high-heeled and narrow-toed shoes, use of a metatarsal bar or pad, cushioning sleeves or stocking caps with silicon linings, and a longitudinal pad beneath the toes.

Complete recommendations on achieving glycemic control in T2D can be found in the 2022 American Diabetes Association Standards of Medical Care. Guidelines on foot care are also available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical findings are consistent with a diagnosis of claw toe, which can be caused by diabetes-related peripheral neuropathy.

According to the International Diabetes Federation, diabetes currently affects approximately 537 million adults worldwide. The number of individuals living with diabetes is expected to exceed 640 million by 2030 and 780 million by 2045. In the United States, more than 37 million people are living with diabetes.

Foot complications related to diabetes represent a significant economic and social burden and can profoundly affect a patient's quality of life and medical outcomes. Common diabetes-related foot complications include foot deformity and peripheral neuropathy, both of which increase the risk for ulceration and amputation. The most common deformity is at the metatarsophalangeal joint (MTPJ). As many as 85% of patients with a history of ulcers and amputation have an MTPJ deformity such as claw toe or hammertoe.

Although they are often grouped together, claw toe and hammertoe have distinct features. Extended MTPJ, flexed proximal interphalangeal joint (PIPJ), and flexed distal interphalangeal joint (DIPJ) are characteristic of claw toe. While hammertoe also has extended MTPJ and flexed PIPJ, the DIPJ is extended rather than flexed. In both cases, the area of high pressure at risk for skin breakdown and ulceration is at the metatarsal head as a result of MTPJ hyperextension deformity. 

Prompt detection and care of diabetes-related foot complications can minimize progression and negative consequences on patients' health and quality of life. According to the American Diabetes Association, all patients with diabetes should undergo a comprehensive foot evaluation at least annually to identify risk factors for ulceration and amputation, which include foot deformities, poor glycemic control, peripheral neuropathy, cigarette smoking, preulcerative callus or corn, peripheral artery disease, chronic kidney disease, visual impairment, and a history of ulceration or amputation. When patients present with a history of ulceration or amputation, a foot inspection should be conducted at each visit. 

A comprehensive foot evaluation should include inspection of the skin, evaluation of any foot deformities, a neurologic assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature, vibration), and a vascular assessment, including pulses in the legs and feet.

Patients should be educated on risk factors and appropriate management of foot-related complications, including the importance of effective glycemic control and daily monitoring of feet. Treatment may be medical, surgical, or both, as indicated by the individual patient's presentation. Conservative treatment approaches include footwear that is extra wide or deep, avoiding high-heeled and narrow-toed shoes, use of a metatarsal bar or pad, cushioning sleeves or stocking caps with silicon linings, and a longitudinal pad beneath the toes.

Complete recommendations on achieving glycemic control in T2D can be found in the 2022 American Diabetes Association Standards of Medical Care. Guidelines on foot care are also available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

This patient's physical findings are consistent with a diagnosis of claw toe, which can be caused by diabetes-related peripheral neuropathy.

According to the International Diabetes Federation, diabetes currently affects approximately 537 million adults worldwide. The number of individuals living with diabetes is expected to exceed 640 million by 2030 and 780 million by 2045. In the United States, more than 37 million people are living with diabetes.

Foot complications related to diabetes represent a significant economic and social burden and can profoundly affect a patient's quality of life and medical outcomes. Common diabetes-related foot complications include foot deformity and peripheral neuropathy, both of which increase the risk for ulceration and amputation. The most common deformity is at the metatarsophalangeal joint (MTPJ). As many as 85% of patients with a history of ulcers and amputation have an MTPJ deformity such as claw toe or hammertoe.

Although they are often grouped together, claw toe and hammertoe have distinct features. Extended MTPJ, flexed proximal interphalangeal joint (PIPJ), and flexed distal interphalangeal joint (DIPJ) are characteristic of claw toe. While hammertoe also has extended MTPJ and flexed PIPJ, the DIPJ is extended rather than flexed. In both cases, the area of high pressure at risk for skin breakdown and ulceration is at the metatarsal head as a result of MTPJ hyperextension deformity. 

Prompt detection and care of diabetes-related foot complications can minimize progression and negative consequences on patients' health and quality of life. According to the American Diabetes Association, all patients with diabetes should undergo a comprehensive foot evaluation at least annually to identify risk factors for ulceration and amputation, which include foot deformities, poor glycemic control, peripheral neuropathy, cigarette smoking, preulcerative callus or corn, peripheral artery disease, chronic kidney disease, visual impairment, and a history of ulceration or amputation. When patients present with a history of ulceration or amputation, a foot inspection should be conducted at each visit. 

A comprehensive foot evaluation should include inspection of the skin, evaluation of any foot deformities, a neurologic assessment (10-g monofilament testing with at least one other assessment: pinprick, temperature, vibration), and a vascular assessment, including pulses in the legs and feet.

Patients should be educated on risk factors and appropriate management of foot-related complications, including the importance of effective glycemic control and daily monitoring of feet. Treatment may be medical, surgical, or both, as indicated by the individual patient's presentation. Conservative treatment approaches include footwear that is extra wide or deep, avoiding high-heeled and narrow-toed shoes, use of a metatarsal bar or pad, cushioning sleeves or stocking caps with silicon linings, and a longitudinal pad beneath the toes.

Complete recommendations on achieving glycemic control in T2D can be found in the 2022 American Diabetes Association Standards of Medical Care. Guidelines on foot care are also available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The American Diabetes Association (ADA) position statement on diabetic retinopathy states that hyperglycemia has been the most consistently associated risk factor for retinopathy. A large and consistent set of observational studies and clinical trials confirms the association of poor glucose control and retinopathy. 

The Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial of intensive glycemic control vs conventional glycemic control in people with type 1 diabetes (T1D), demonstrated that intensive therapy reduced the development or progression of diabetic retinopathy by 34%-76%. The DCCT also demonstrated a definitive relationship between hyperglycemia and diabetic microvascular complications, including retinopathy. Early treatment with intensive therapy was effective.

The UK Prospective Diabetes Study (UKPDS) of patients with newly diagnosed T2D conclusively demonstrated that improved blood glucose control reduced the risk for retinopathy and nephropathy and, possibly, neuropathy. The overall microvascular complication rate was decreased by 25% in patients receiving intensive therapy vs conventional therapy. Epidemiologic analysis of the UKPDS data showed a continuous relationship between the risk for microvascular complications and glycemia, such that every percentage-point decrease in A1c (eg, 9% to 8%) was associated with a 35% reduction in the risk for microvascular complications.

More recently, the ACCORD trial of medical therapies demonstrated that intensive glycemic control reduced the risk for progression of diabetic retinopathy in people with T2D of 10 years' duration. This study included 2856 ACCORD participants enrolled in the ACCORD Eye Study and followed for 4 years.

The ADA recommends screening by an ophthalmologist for diabetic retinopathy within 5 years of the diagnosis of T1D and at the time of diagnosis of T2D. Women with preexisting diabetes who are planning pregnancy or who have become pregnant should be screened before pregnancy or in the first trimester.

While optimization of blood glucose, blood pressure, and serum lipid levels in conjunction with appropriately scheduled dilated eye examinations can substantially decrease the risk for vision loss from diabetic retinopathy, a significant proportion of those affected with diabetes develop diabetic macular edema or proliferative changes that require intervention. ADA treatment recommendations are:

•    Refer patients with any level of macular edema, severe nonproliferative diabetic retinopathy (a precursor of proliferative diabetic retinopathy), or proliferative diabetic retinopathy to an ophthalmologist knowledgeable and experienced in the management and treatment of diabetic retinopathy.
•    Laser photocoagulation therapy reduces the risk for vision loss in patients with high-risk proliferative diabetic retinopathy and, in some cases, severe nonproliferative diabetic retinopathy.
•    Intravitreous injections of anti–vascular endothelial growth factor are indicated for central-involved diabetic macular edema, which occurs beneath the foveal center and may threaten reading vision.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The American Diabetes Association (ADA) position statement on diabetic retinopathy states that hyperglycemia has been the most consistently associated risk factor for retinopathy. A large and consistent set of observational studies and clinical trials confirms the association of poor glucose control and retinopathy. 

The Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial of intensive glycemic control vs conventional glycemic control in people with type 1 diabetes (T1D), demonstrated that intensive therapy reduced the development or progression of diabetic retinopathy by 34%-76%. The DCCT also demonstrated a definitive relationship between hyperglycemia and diabetic microvascular complications, including retinopathy. Early treatment with intensive therapy was effective.

The UK Prospective Diabetes Study (UKPDS) of patients with newly diagnosed T2D conclusively demonstrated that improved blood glucose control reduced the risk for retinopathy and nephropathy and, possibly, neuropathy. The overall microvascular complication rate was decreased by 25% in patients receiving intensive therapy vs conventional therapy. Epidemiologic analysis of the UKPDS data showed a continuous relationship between the risk for microvascular complications and glycemia, such that every percentage-point decrease in A1c (eg, 9% to 8%) was associated with a 35% reduction in the risk for microvascular complications.

More recently, the ACCORD trial of medical therapies demonstrated that intensive glycemic control reduced the risk for progression of diabetic retinopathy in people with T2D of 10 years' duration. This study included 2856 ACCORD participants enrolled in the ACCORD Eye Study and followed for 4 years.

The ADA recommends screening by an ophthalmologist for diabetic retinopathy within 5 years of the diagnosis of T1D and at the time of diagnosis of T2D. Women with preexisting diabetes who are planning pregnancy or who have become pregnant should be screened before pregnancy or in the first trimester.

While optimization of blood glucose, blood pressure, and serum lipid levels in conjunction with appropriately scheduled dilated eye examinations can substantially decrease the risk for vision loss from diabetic retinopathy, a significant proportion of those affected with diabetes develop diabetic macular edema or proliferative changes that require intervention. ADA treatment recommendations are:

•    Refer patients with any level of macular edema, severe nonproliferative diabetic retinopathy (a precursor of proliferative diabetic retinopathy), or proliferative diabetic retinopathy to an ophthalmologist knowledgeable and experienced in the management and treatment of diabetic retinopathy.
•    Laser photocoagulation therapy reduces the risk for vision loss in patients with high-risk proliferative diabetic retinopathy and, in some cases, severe nonproliferative diabetic retinopathy.
•    Intravitreous injections of anti–vascular endothelial growth factor are indicated for central-involved diabetic macular edema, which occurs beneath the foveal center and may threaten reading vision.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The American Diabetes Association (ADA) position statement on diabetic retinopathy states that hyperglycemia has been the most consistently associated risk factor for retinopathy. A large and consistent set of observational studies and clinical trials confirms the association of poor glucose control and retinopathy. 

The Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial of intensive glycemic control vs conventional glycemic control in people with type 1 diabetes (T1D), demonstrated that intensive therapy reduced the development or progression of diabetic retinopathy by 34%-76%. The DCCT also demonstrated a definitive relationship between hyperglycemia and diabetic microvascular complications, including retinopathy. Early treatment with intensive therapy was effective.

The UK Prospective Diabetes Study (UKPDS) of patients with newly diagnosed T2D conclusively demonstrated that improved blood glucose control reduced the risk for retinopathy and nephropathy and, possibly, neuropathy. The overall microvascular complication rate was decreased by 25% in patients receiving intensive therapy vs conventional therapy. Epidemiologic analysis of the UKPDS data showed a continuous relationship between the risk for microvascular complications and glycemia, such that every percentage-point decrease in A1c (eg, 9% to 8%) was associated with a 35% reduction in the risk for microvascular complications.

More recently, the ACCORD trial of medical therapies demonstrated that intensive glycemic control reduced the risk for progression of diabetic retinopathy in people with T2D of 10 years' duration. This study included 2856 ACCORD participants enrolled in the ACCORD Eye Study and followed for 4 years.

The ADA recommends screening by an ophthalmologist for diabetic retinopathy within 5 years of the diagnosis of T1D and at the time of diagnosis of T2D. Women with preexisting diabetes who are planning pregnancy or who have become pregnant should be screened before pregnancy or in the first trimester.

While optimization of blood glucose, blood pressure, and serum lipid levels in conjunction with appropriately scheduled dilated eye examinations can substantially decrease the risk for vision loss from diabetic retinopathy, a significant proportion of those affected with diabetes develop diabetic macular edema or proliferative changes that require intervention. ADA treatment recommendations are:

•    Refer patients with any level of macular edema, severe nonproliferative diabetic retinopathy (a precursor of proliferative diabetic retinopathy), or proliferative diabetic retinopathy to an ophthalmologist knowledgeable and experienced in the management and treatment of diabetic retinopathy.
•    Laser photocoagulation therapy reduces the risk for vision loss in patients with high-risk proliferative diabetic retinopathy and, in some cases, severe nonproliferative diabetic retinopathy.
•    Intravitreous injections of anti–vascular endothelial growth factor are indicated for central-involved diabetic macular edema, which occurs beneath the foveal center and may threaten reading vision.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The 2020 Kidney Disease Improving Global Outcomes (KDIGO) diabetes management in CKD guideline states that most patients with diabetic nephropathy and an eGFR  ≥ 30 mL/min/1.73 m² benefit from treatment with both metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which have been demonstrated to offer substantial benefits in reducing the risks for diabetic nephropathy and cardiovascular disease.

In patients who do not reach individualized targets with metformin and an SGLT2 inhibitor, or who are unable to use these medications, a long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist may be used.

Metformin should be administered with caution to patients with CKD because it may increase the risk for lactic acidosis. It is contraindicated in patients with an eGFR < 30, but this patient's eGFR is adequate. Many clinicians might use a lower metformin dosage (1500 mg) as a precaution. Given how high his A1c is, adding a GLP-1 receptor antagonist is probably going to be needed because an SGLT2 inhibitor is only intermediate in terms of glucose reduction. 

For control of his hypertension, the American Diabetes Association recommends either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) as first-line treatment. However, one agent alone is unlikely to control this patient's hypertension. At his level of eGFR, a thiazide diuretic is unlikely to be very effective. Therefore, a loop diuretic should be initiated with the ACE inhibitor or ARB, especially because he has edema.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The 2020 Kidney Disease Improving Global Outcomes (KDIGO) diabetes management in CKD guideline states that most patients with diabetic nephropathy and an eGFR  ≥ 30 mL/min/1.73 m² benefit from treatment with both metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which have been demonstrated to offer substantial benefits in reducing the risks for diabetic nephropathy and cardiovascular disease.

In patients who do not reach individualized targets with metformin and an SGLT2 inhibitor, or who are unable to use these medications, a long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist may be used.

Metformin should be administered with caution to patients with CKD because it may increase the risk for lactic acidosis. It is contraindicated in patients with an eGFR < 30, but this patient's eGFR is adequate. Many clinicians might use a lower metformin dosage (1500 mg) as a precaution. Given how high his A1c is, adding a GLP-1 receptor antagonist is probably going to be needed because an SGLT2 inhibitor is only intermediate in terms of glucose reduction. 

For control of his hypertension, the American Diabetes Association recommends either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) as first-line treatment. However, one agent alone is unlikely to control this patient's hypertension. At his level of eGFR, a thiazide diuretic is unlikely to be very effective. Therefore, a loop diuretic should be initiated with the ACE inhibitor or ARB, especially because he has edema.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The 2020 Kidney Disease Improving Global Outcomes (KDIGO) diabetes management in CKD guideline states that most patients with diabetic nephropathy and an eGFR  ≥ 30 mL/min/1.73 m² benefit from treatment with both metformin and a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which have been demonstrated to offer substantial benefits in reducing the risks for diabetic nephropathy and cardiovascular disease.

In patients who do not reach individualized targets with metformin and an SGLT2 inhibitor, or who are unable to use these medications, a long-acting glucagon-like peptide 1 (GLP-1) receptor antagonist may be used.

Metformin should be administered with caution to patients with CKD because it may increase the risk for lactic acidosis. It is contraindicated in patients with an eGFR < 30, but this patient's eGFR is adequate. Many clinicians might use a lower metformin dosage (1500 mg) as a precaution. Given how high his A1c is, adding a GLP-1 receptor antagonist is probably going to be needed because an SGLT2 inhibitor is only intermediate in terms of glucose reduction. 

For control of his hypertension, the American Diabetes Association recommends either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) as first-line treatment. However, one agent alone is unlikely to control this patient's hypertension. At his level of eGFR, a thiazide diuretic is unlikely to be very effective. Therefore, a loop diuretic should be initiated with the ACE inhibitor or ARB, especially because he has edema.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.
 

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

PCOS is most often defined according to the Rotterdam criteria, which stipulate that at least two of the following be present: irregular ovulation, biochemical/clinical hyperandrogenism, and polycystic ovaries (seen in the MRI scan above). Insulin resistance is part of the pathogenesis of PCOS, and insulin resistance is associated with T2D in PCOS. 

In fact, PCOS is an independent risk factor for T2D, even after adjustment for BMI and obesity. Even normal-weight women with PCOS have an increased risk for T2D. More than half of women with PCOS develop T2D by age 40. 

Even though family history and obesity are major contributors in the development of diabetes in patients with PCOS, diabetes can still occur in lean patients with PCOS who have no family history, mainly secondary to insulin resistance.

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test every 3-5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity. In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, an annual oral glucose tolerance test is recommended for patients with PCOS and impaired glucose tolerance, whereas those with a family history of T2D or a BMI above 30 should be screened every 1-2 years.

Management of T2D with PCOS is similar to that of T2D without PCOS. Accordingly, metformin and lifestyle changes are the treatments of choice; any antidiabetic agent may be added in patients who do not achieve glycemic targets despite treatment with metformin.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

PCOS is most often defined according to the Rotterdam criteria, which stipulate that at least two of the following be present: irregular ovulation, biochemical/clinical hyperandrogenism, and polycystic ovaries (seen in the MRI scan above). Insulin resistance is part of the pathogenesis of PCOS, and insulin resistance is associated with T2D in PCOS. 

In fact, PCOS is an independent risk factor for T2D, even after adjustment for BMI and obesity. Even normal-weight women with PCOS have an increased risk for T2D. More than half of women with PCOS develop T2D by age 40. 

Even though family history and obesity are major contributors in the development of diabetes in patients with PCOS, diabetes can still occur in lean patients with PCOS who have no family history, mainly secondary to insulin resistance.

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test every 3-5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity. In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, an annual oral glucose tolerance test is recommended for patients with PCOS and impaired glucose tolerance, whereas those with a family history of T2D or a BMI above 30 should be screened every 1-2 years.

Management of T2D with PCOS is similar to that of T2D without PCOS. Accordingly, metformin and lifestyle changes are the treatments of choice; any antidiabetic agent may be added in patients who do not achieve glycemic targets despite treatment with metformin.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

PCOS is most often defined according to the Rotterdam criteria, which stipulate that at least two of the following be present: irregular ovulation, biochemical/clinical hyperandrogenism, and polycystic ovaries (seen in the MRI scan above). Insulin resistance is part of the pathogenesis of PCOS, and insulin resistance is associated with T2D in PCOS. 

In fact, PCOS is an independent risk factor for T2D, even after adjustment for BMI and obesity. Even normal-weight women with PCOS have an increased risk for T2D. More than half of women with PCOS develop T2D by age 40. 

Even though family history and obesity are major contributors in the development of diabetes in patients with PCOS, diabetes can still occur in lean patients with PCOS who have no family history, mainly secondary to insulin resistance.

The Endocrine Society recommends that all individuals with PCOS undergo an oral glucose tolerance test every 3-5 years, with more frequent screening for those who develop symptoms of T2D, significant weight gain, or central adiposity. In guidelines published in 2015 by the American Association of Clinical Endocrinologists, the American College of Endocrinology, and the Androgen Excess and PCOS Society, an annual oral glucose tolerance test is recommended for patients with PCOS and impaired glucose tolerance, whereas those with a family history of T2D or a BMI above 30 should be screened every 1-2 years.

Management of T2D with PCOS is similar to that of T2D without PCOS. Accordingly, metformin and lifestyle changes are the treatments of choice; any antidiabetic agent may be added in patients who do not achieve glycemic targets despite treatment with metformin.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

The patient's clinical presentation and laboratory findings are consistent with a diagnosis of T2D.

The prevalence of T2D is increasing dramatically in children and adolescents. Like adult-onset T2D, obesity, family history, and sedentary lifestyle are major predisposing risk factors for T2D in children and adolescents. Significantly, the onset of diabetes at a younger age is associated with longer disease exposure and increased risk for chronic complications. Moreover, T2D in adolescents manifests as a severe progressive phenotype that often presents with complications, poor treatment response, and rapid progression of microvascular and macrovascular complications. Studies have shown that the risk for complications is greater in youth-onset T2D than it is in type 1 diabetes (T1D) and adult-onset T2D. 

T2D has a variable presentation in children and adolescents. Approximately one third of patients are diagnosed without having typical diabetes signs or symptoms. In most cases, these patients are in their mid-adolescence are obese and were screened because of one or more positive risk factors or because glycosuria was detected on a random urine test. These patients typically have one or more of the typical characteristics of metabolic syndrome, such as hypertension and dyslipidemia. 

Polyuria and polydipsia are seen in approximately 67% of youth with T2D at presentation. Recent weight loss may be present, but it is usually less severe in patients with T2D compared with T1D. Additionally, frequent fungal skin infections or severe vulvovaginitis because of Candida in adolescent girls can be the presenting complaint.

Diabetic ketoacidosis is present in less than 1 in 10 adolescents diagnosed with T2D. Most of these patients belong to ethnic minority groups, report polyuria, polydipsia, fatigue, and lethargy, and require hospital admission, rehydration, and insulin replacement therapy. Patients with symptoms such as vomiting can decline rapidly and need urgent evaluation and management. 

Certain adolescent patients with obesity who present with diabetic ketoacidosis and are diagnosed with T2D at presentation can also have T1D and will require lifelong insulin treatment. Therefore, following a diagnosis of diabetes in an adolescent, it is critical to differentiate T2D from type 1 diabetes, as well as from other more rare diabetes types, to ensure proper long-term management. Given the substantial overlap between T2D and T1D symptoms, a combination of history clues, clinical characteristics, and laboratory studies must be used to reliably make the distinction. Important clues in the patient's history include:

•    Age. Patients with T2D typically present after the onset of puberty, at a mean age of 13.5 years. Conversely, nearly one half of patients with T1D present before 10 years of age, regardless of race or ethnicity. 
•    Family history. Up to 90% of patients with T2D have an affected first- or second-degree relative; the corresponding percentage for patients with T1D is less than 10%.
•    Ethnicity. T2D disproportionately affects youth of ethnic and racial minorities. Compared with White individuals, youth belonging to minority groups such as Native American, African American, Hispanic, and Pacific Islander have a much higher risk of developing T2D.
•    Body weight. Most adolescents with T2D have obesity (BMI ≥ 95 percentile for age and sex), whereas those with T1D are usually of normal weight and may report a recent history of weight loss.
•    Clinical findings. Adolescents with T2D usually present with features of insulin resistance and metabolic syndrome, such as acanthosis nigricans, hypertension, dyslipidemia, and polycystic ovary syndrome, whereas these findings are rare in youth with T1D. One study showed that up to 90% of youth diagnosed with T2D had acanthosis nigricans, in contrast to only 12% of those diagnosed with T1D. 

Additionally, when the diagnosis of T2D is being considered in children and adolescents, a panel of pancreatic autoantibodies should be tested to exclude the possibility of autoimmune T1D. Because T2D is not immunologically mediated, the identification of one or more pancreatic (islet) cell antibodies in a diabetic adolescent with obesity supports the diagnosis of autoimmune diabetes. Antibodies that are usually measured include islet cell antibodies (against cytoplasmic proteins in the beta cell), anti-glutamic acid decarboxylase, and tyrosine phosphatase insulinoma-associated antigen 2, as well as anti-insulin antibodies if insulin replacement therapy has not been used for more than 2 weeks. In addition, a beta cell–specific autoantibody to zinc transporter 8 is frequently detected in children with T1D and can aid in the differential diagnosis. However, up to one third of children with T2D can have at least one detectable beta-cell autoantibody; therefore, total absence of diabetes autoimmune markers is not required for the diagnosis of T2D in children and adolescents.

When a diagnosis of T2D has been established, treatment should consist of lifestyle management, diabetes self-management education, and pharmacologic therapy. According to the 2022 American Diabetes Association Standards of Medical Care, the management of diabetes in children and adolescents cannot simply be drawn from the typical care provided to adults with diabetes. The epidemiology, pathophysiology, developmental considerations, and response to therapy in pediatric populations often vary from adult diabetes, and differences exist in recommended care for children and adolescents with T1D, T2D, and other forms of pediatric diabetes. 

Because the diabetes type is often uncertain in the first few weeks of treatment, initial therapy should address the hyperglycemia and associated metabolic derangements regardless of the ultimate diabetes type; therapy should then be adjusted once metabolic compensation has been established and subsequent information, such as islet autoantibody results, becomes available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

The patient's clinical presentation and laboratory findings are consistent with a diagnosis of T2D.

The prevalence of T2D is increasing dramatically in children and adolescents. Like adult-onset T2D, obesity, family history, and sedentary lifestyle are major predisposing risk factors for T2D in children and adolescents. Significantly, the onset of diabetes at a younger age is associated with longer disease exposure and increased risk for chronic complications. Moreover, T2D in adolescents manifests as a severe progressive phenotype that often presents with complications, poor treatment response, and rapid progression of microvascular and macrovascular complications. Studies have shown that the risk for complications is greater in youth-onset T2D than it is in type 1 diabetes (T1D) and adult-onset T2D. 

T2D has a variable presentation in children and adolescents. Approximately one third of patients are diagnosed without having typical diabetes signs or symptoms. In most cases, these patients are in their mid-adolescence are obese and were screened because of one or more positive risk factors or because glycosuria was detected on a random urine test. These patients typically have one or more of the typical characteristics of metabolic syndrome, such as hypertension and dyslipidemia. 

Polyuria and polydipsia are seen in approximately 67% of youth with T2D at presentation. Recent weight loss may be present, but it is usually less severe in patients with T2D compared with T1D. Additionally, frequent fungal skin infections or severe vulvovaginitis because of Candida in adolescent girls can be the presenting complaint.

Diabetic ketoacidosis is present in less than 1 in 10 adolescents diagnosed with T2D. Most of these patients belong to ethnic minority groups, report polyuria, polydipsia, fatigue, and lethargy, and require hospital admission, rehydration, and insulin replacement therapy. Patients with symptoms such as vomiting can decline rapidly and need urgent evaluation and management. 

Certain adolescent patients with obesity who present with diabetic ketoacidosis and are diagnosed with T2D at presentation can also have T1D and will require lifelong insulin treatment. Therefore, following a diagnosis of diabetes in an adolescent, it is critical to differentiate T2D from type 1 diabetes, as well as from other more rare diabetes types, to ensure proper long-term management. Given the substantial overlap between T2D and T1D symptoms, a combination of history clues, clinical characteristics, and laboratory studies must be used to reliably make the distinction. Important clues in the patient's history include:

•    Age. Patients with T2D typically present after the onset of puberty, at a mean age of 13.5 years. Conversely, nearly one half of patients with T1D present before 10 years of age, regardless of race or ethnicity. 
•    Family history. Up to 90% of patients with T2D have an affected first- or second-degree relative; the corresponding percentage for patients with T1D is less than 10%.
•    Ethnicity. T2D disproportionately affects youth of ethnic and racial minorities. Compared with White individuals, youth belonging to minority groups such as Native American, African American, Hispanic, and Pacific Islander have a much higher risk of developing T2D.
•    Body weight. Most adolescents with T2D have obesity (BMI ≥ 95 percentile for age and sex), whereas those with T1D are usually of normal weight and may report a recent history of weight loss.
•    Clinical findings. Adolescents with T2D usually present with features of insulin resistance and metabolic syndrome, such as acanthosis nigricans, hypertension, dyslipidemia, and polycystic ovary syndrome, whereas these findings are rare in youth with T1D. One study showed that up to 90% of youth diagnosed with T2D had acanthosis nigricans, in contrast to only 12% of those diagnosed with T1D. 

Additionally, when the diagnosis of T2D is being considered in children and adolescents, a panel of pancreatic autoantibodies should be tested to exclude the possibility of autoimmune T1D. Because T2D is not immunologically mediated, the identification of one or more pancreatic (islet) cell antibodies in a diabetic adolescent with obesity supports the diagnosis of autoimmune diabetes. Antibodies that are usually measured include islet cell antibodies (against cytoplasmic proteins in the beta cell), anti-glutamic acid decarboxylase, and tyrosine phosphatase insulinoma-associated antigen 2, as well as anti-insulin antibodies if insulin replacement therapy has not been used for more than 2 weeks. In addition, a beta cell–specific autoantibody to zinc transporter 8 is frequently detected in children with T1D and can aid in the differential diagnosis. However, up to one third of children with T2D can have at least one detectable beta-cell autoantibody; therefore, total absence of diabetes autoimmune markers is not required for the diagnosis of T2D in children and adolescents.

When a diagnosis of T2D has been established, treatment should consist of lifestyle management, diabetes self-management education, and pharmacologic therapy. According to the 2022 American Diabetes Association Standards of Medical Care, the management of diabetes in children and adolescents cannot simply be drawn from the typical care provided to adults with diabetes. The epidemiology, pathophysiology, developmental considerations, and response to therapy in pediatric populations often vary from adult diabetes, and differences exist in recommended care for children and adolescents with T1D, T2D, and other forms of pediatric diabetes. 

Because the diabetes type is often uncertain in the first few weeks of treatment, initial therapy should address the hyperglycemia and associated metabolic derangements regardless of the ultimate diabetes type; therapy should then be adjusted once metabolic compensation has been established and subsequent information, such as islet autoantibody results, becomes available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships

The patient's clinical presentation and laboratory findings are consistent with a diagnosis of T2D.

The prevalence of T2D is increasing dramatically in children and adolescents. Like adult-onset T2D, obesity, family history, and sedentary lifestyle are major predisposing risk factors for T2D in children and adolescents. Significantly, the onset of diabetes at a younger age is associated with longer disease exposure and increased risk for chronic complications. Moreover, T2D in adolescents manifests as a severe progressive phenotype that often presents with complications, poor treatment response, and rapid progression of microvascular and macrovascular complications. Studies have shown that the risk for complications is greater in youth-onset T2D than it is in type 1 diabetes (T1D) and adult-onset T2D. 

T2D has a variable presentation in children and adolescents. Approximately one third of patients are diagnosed without having typical diabetes signs or symptoms. In most cases, these patients are in their mid-adolescence are obese and were screened because of one or more positive risk factors or because glycosuria was detected on a random urine test. These patients typically have one or more of the typical characteristics of metabolic syndrome, such as hypertension and dyslipidemia. 

Polyuria and polydipsia are seen in approximately 67% of youth with T2D at presentation. Recent weight loss may be present, but it is usually less severe in patients with T2D compared with T1D. Additionally, frequent fungal skin infections or severe vulvovaginitis because of Candida in adolescent girls can be the presenting complaint.

Diabetic ketoacidosis is present in less than 1 in 10 adolescents diagnosed with T2D. Most of these patients belong to ethnic minority groups, report polyuria, polydipsia, fatigue, and lethargy, and require hospital admission, rehydration, and insulin replacement therapy. Patients with symptoms such as vomiting can decline rapidly and need urgent evaluation and management. 

Certain adolescent patients with obesity who present with diabetic ketoacidosis and are diagnosed with T2D at presentation can also have T1D and will require lifelong insulin treatment. Therefore, following a diagnosis of diabetes in an adolescent, it is critical to differentiate T2D from type 1 diabetes, as well as from other more rare diabetes types, to ensure proper long-term management. Given the substantial overlap between T2D and T1D symptoms, a combination of history clues, clinical characteristics, and laboratory studies must be used to reliably make the distinction. Important clues in the patient's history include:

•    Age. Patients with T2D typically present after the onset of puberty, at a mean age of 13.5 years. Conversely, nearly one half of patients with T1D present before 10 years of age, regardless of race or ethnicity. 
•    Family history. Up to 90% of patients with T2D have an affected first- or second-degree relative; the corresponding percentage for patients with T1D is less than 10%.
•    Ethnicity. T2D disproportionately affects youth of ethnic and racial minorities. Compared with White individuals, youth belonging to minority groups such as Native American, African American, Hispanic, and Pacific Islander have a much higher risk of developing T2D.
•    Body weight. Most adolescents with T2D have obesity (BMI ≥ 95 percentile for age and sex), whereas those with T1D are usually of normal weight and may report a recent history of weight loss.
•    Clinical findings. Adolescents with T2D usually present with features of insulin resistance and metabolic syndrome, such as acanthosis nigricans, hypertension, dyslipidemia, and polycystic ovary syndrome, whereas these findings are rare in youth with T1D. One study showed that up to 90% of youth diagnosed with T2D had acanthosis nigricans, in contrast to only 12% of those diagnosed with T1D. 

Additionally, when the diagnosis of T2D is being considered in children and adolescents, a panel of pancreatic autoantibodies should be tested to exclude the possibility of autoimmune T1D. Because T2D is not immunologically mediated, the identification of one or more pancreatic (islet) cell antibodies in a diabetic adolescent with obesity supports the diagnosis of autoimmune diabetes. Antibodies that are usually measured include islet cell antibodies (against cytoplasmic proteins in the beta cell), anti-glutamic acid decarboxylase, and tyrosine phosphatase insulinoma-associated antigen 2, as well as anti-insulin antibodies if insulin replacement therapy has not been used for more than 2 weeks. In addition, a beta cell–specific autoantibody to zinc transporter 8 is frequently detected in children with T1D and can aid in the differential diagnosis. However, up to one third of children with T2D can have at least one detectable beta-cell autoantibody; therefore, total absence of diabetes autoimmune markers is not required for the diagnosis of T2D in children and adolescents.

When a diagnosis of T2D has been established, treatment should consist of lifestyle management, diabetes self-management education, and pharmacologic therapy. According to the 2022 American Diabetes Association Standards of Medical Care, the management of diabetes in children and adolescents cannot simply be drawn from the typical care provided to adults with diabetes. The epidemiology, pathophysiology, developmental considerations, and response to therapy in pediatric populations often vary from adult diabetes, and differences exist in recommended care for children and adolescents with T1D, T2D, and other forms of pediatric diabetes. 

Because the diabetes type is often uncertain in the first few weeks of treatment, initial therapy should address the hyperglycemia and associated metabolic derangements regardless of the ultimate diabetes type; therapy should then be adjusted once metabolic compensation has been established and subsequent information, such as islet autoantibody results, becomes available.

Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia

Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships