Insulin-based versus triple oral therapy for newly diagnosed type 2 diabetes: which is better?

OBJECTIVE: Early use of insulin after diagnosis of type 2 diabetes is met with resistance because of associated weight gain, hypoglycemia, and fear of decreased compliance and quality of life (QoL). RESEARCH DESIGN AND METHODS: In treatment-naive patients with newly diagnosed type 2 diabetes, insulin and metformin were initiated for a 3-month lead-in period, then patients were randomly assigned to insulin and metformin (insulin group) or metformin, pioglitazone, and glyburide (oral group) for 36 months. Hypoglycemic events, compliance, A1C, weight, QoL, and treatment satisfaction were assessed. RESULTS: Of 29 patients randomly assigned into each group, 83% (insulin group) and 72% (oral group) completed this 3-year study. At study completion, A1C was 6.1 +/- 0.6% (insulin group) versus 6.0 +/- 0.8% (oral group). Weight increased similarly in both groups (P = 0.09) by 4.47 kg (95% CI 0.89-8.04 kg) (insulin group) and 7.15 kg (95% CI 4.18-10.13 kg) (orals group). Hypoglycemic events did not differ between groups (mild 0.51 event/person-month in the insulin group vs. 0.68 event/person-month in the orals group, P = 0.18 and severe 0.04 event/person-year in the insulin group vs. 0.09 event/person-year in the orals group, P = 0.53). Compliance, QoL, and treatment satisfaction were similar between groups, with 100% of patients randomly assigned to insulin willing to continue such treatment. CONCLUSIONS: When compared with a clinically equivalent treatment regimen, insulin-based therapy is effective and did not cause greater weight gain or hypoglycemia nor decrease compliance, treatment satisfaction, or QoL. Insulin is safe, well-accepted, and effective for ongoing treatment of patients with newly diagnosed type 2 diabetes.

Noninvasive quantification of pancreatic fat in humans.

OBJECTIVE: To validate magnetic resonance spectroscopy (MRS) as a tool for non-invasive quantification of pancreatic triglyceride (TG) content and to measure the pancreatic TG content in a diverse human population with a wide range of body mass index (BMI) and glucose control. METHODS: To validate the MRS method, we measured TG content in the pancreatic tissue of 12 lean and 12 fatty ZDF rats (ages 5-14 weeks) both by MRS and the gold standard biochemical assay. We used MRS to measure pancreatic TG content in vivo in 79 human volunteers. Additionally, to assess the reproducibility of the method, in 33 volunteers we obtained duplicate MRS measurements 1-2 weeks apart. RESULTS: MRS quantifies pancreatic TG content with high reproducibility and concordance to the biochemical measurement (Spearman's rank correlation coefficient = 0.91). In humans, median pancreatic TG content was as follows: (1) normal weight and normoglycemic group 0.46 f/w%, (2) overweight or obese but normoglycemic group 3.16 f/w%, (3) impaired fasting glucose or impaired glucose tolerance group (BMI matched with group 2) 5.64 f/w%, and (4) untreated type 2 diabetes group (BMI matched with group 2) 5.54 f/w% (Jonckheere-Terpstra trend test across groups p < 0.001). CONCLUSIONS: Human pancreatic steatosis, as measured by MRS, increases with BMI and with impaired glycemia. MRS is a quantitative and reproducible non-invasive clinical research tool which will enable systematic studies of the relationship between ectopic fat accumulation in the pancreas and development of type 2 diabetes.