One motivation to study autoantibody testing is a potential benefit in preserving pancreatic function. Kobayashi proposed treating those with autoantibody-positive diabetes (presumed type 1 or type 1.5) with insulin immediately, while initiating oral medications in those who test negative (presumed type 2 diabetes). This approach lacks significant patient-oriented outcome data, but his small RCT of 55 patients was encouraging. With a 3-year follow-up rate of 89%, early insulin use in GADAb+ patients preserved C-peptide levels and possibly prolonged pancreatic beta cell survival.7 Insulin dependency, defined as needing insulin for survival, occurred in 47% of controls (who received oral sulfonylureas) and only 13% of patients receiving insulin (number needed to treat [NNT]= 4; P=.043).7 The theoretical benefit is that if beta cell exhaustion can be delayed, endogenous insulin production could be maintained to assist prevention of damaging postprandial glucose spikes.
Although daily variation in serum insulin levels limits its use, C-peptide levels show more promise. Random C-peptide levels were superior to fasting or glucagon stimulated levels in 1093 patients, who were followed for 3 years to confirm insulin requirements. Using a receiver operating characteristic (ROC) curve, the area under the curve for random C-peptide levels to distinguish diabetes types was 0.98 (95% CI, 0.97–0.99).8 For patients under the optimal cutoff of 0.5 nmol/L, the positive predictive value was 96% for diagnosing type 1 and the likelihood ratio was 22.5.
Finally, the ratio of adiponectin to leptin hormone may show diagnostic merit. Adipocytes secrete adiponectin which acts as an insulin sensitizer, antiatherogenic and anti-inflammatory agent. Obesity and type 2 phenotype correlate with lower levels of adiponectin, but are associated with higher levels of leptin hormone, another molecule secreted by adipocytes. A recent case-control study of children aged 6 to 21 years analyzed adiponectin and leptin hormone levels in patients with classical type 1 and 2 diabetes, as determined by 2 pediatric endocrinologists; interestingly, 29% of the type 1 patients were autoantibody negative.9 After plotting a ROC curve, they found the area under the curve was 0.97 (95% CI, 0.93–1.00). At an adiponectin-to-leptin ratio cutoff less than 0.7, they found the sensitivity to diagnose type 2 was 88% (95% CI, 64–99%), the specificity was 90% (95% CI, 77–97), and the likelihood ratio for a positive test was 8.8.9
TABLE 1
Antibody markers and diabetes type
| PREVALENCE OF ANY AUTOANTIBODY MARKER | PERCENT |
|---|---|
| Newly diagnosed type 1 (Caucasian) | 73–90 |
| Newly diagnosed type 1 (African or Asian) | 50 |
| Newly diagnosed type 2 (Caucasian) | 3–22 |
| Healthy individuals | 1–2 |
| Source: Wingfield et al 20041 and Maron et al 1996.3 | |
Recommendations from others
The National Academy of Clinical Biochemistry and the American Association of Clinical Endocrinologists recommend against routine testing of insulin, C-peptide, autoantibodies and genetic markers.1,10 Guidelines from the American Diabetes Association admit that many diabetic individuals do not easily fit into a distinct diagnostic category; however, they only provide criteria for the general diagnosis of diabetes, not specific criteria to distinguish type 1 from type 2.11
CLINICAL COMMENTARY
Focus on attaining optimal diabetes control goals as recommended by the ADA
Vincent Lo, MD
St. Elizabeth Family Medicine Residency Program/SUNY Upstate Medical University, Utica, New York
Not long ago, clinicians were advised to avoid the terms type 1 and type 2 diabetes, because they were not very helpful in clinical management of our patients. Instead, it was suggested that we use insulin-dependent or non-insulin-dependent. The rationale is that for patients with diabetes, there is an absolute insulin deficiency due to premature beta-cell failure in type 1 diabetes, as well as a relative insulin deficiency due to insulin resistance in type 2. In addition, studies also suggest that a majority of patients with type 2 diabetes would require some form of exogenous insulin therapy after a duration of 8 to 10 years of their disease. Therefore, distinguishing between types 1 and 2 is neither clinically helpful nor cost-effective, as suggested by current review of the literature. Instead, clinicians should focus on attaining optimal diabetic control goals as recommended by the practice guidelines of management of diabetes mellitus from the ADA. Furthermore, it was also recognized that one of the hurdles of failure to reach the target goal of HbA1C <7.0, among patients with type 2 diabetes is the delayed use of exogenous insulin therapy. Therefore, it is imperative for clinicians to discuss with each patient with a new diagnosis of diabetes, the natural progression of its disease process and its potential need and benefit of exogenous insulin therapy in the near future.
Acknowledgments
The opinions and assertions contained herein are the private views of the author and are not to be construed as official, or as reflecting the views of the US Air Force medical department or the US Air Force at large.