The effects of early short-term insulin treatment vs. glimepiride on beta cell function in newly diagnosed type 2 diabetes with HbA1c above 9.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a complex metabolic impairment. Beta cell (BC) failure is the most challenging among its pathogenetic mechanisms. Recognizing reversible contributors to BC failure could guide individualized approach to early T2D treatment. The aim of this study was to compare early short-term insulin treatment vs. glimepiride, both added to metformin, on BC function, glycemic and lipid control, during 12-month follow-up. METHODS: Eighty newly diagnosed T2D patients, 30-65 years of age, presenting with HbA1c ≥ 9% were enrolled in the study. They were randomly assigned to single-month initial insulin therapy (INS) added to metformin, or to glimepiride and metformin (OAD) as only treatment. Subjects assigned to initial insulin intervention were thereafter switched to OAD. C-peptide (C-Pep) was analyzed at baseline and 2 hours after standardized test meal (STM). All subjects were STM-retested after 3 and 12 months. HbA1c, serum lipids, BMI, HOMA IR, and HOMA B were assessed over follow-up. RESULTS: HbA1c was lower in INS vs OAD at 3-months: 6.26 ± 0.18% vs 6.78 ± 0.10% (p = 0.016), remaining so by 12 months (p =0.056). BMI-adjusted ΔC-Pep was greater in INS vs. OAD at 3 months (4.60 ± 0.59 vs. 3.21 ± 0.34 m2 /kg; p = 0.044), persisting by 12months (4.57 ± 0.56 vs. 3.04 ± 0.34 m2/kg; p = 0.023). Average ΔC-Pep improvement from recruitment to 3 months was 100.8% in INS,vs. 51.3% in OAD. Prevalence of STM-ΔC-Pep response greater than 2.4 ng/mL had risen 3.2-fold by 12 months in the INS, vs. 2.4-fold only in the OAD group (p = 0.018). DISCUSSION: Early short-term insulin intervention in newly diagnosed T2D improves beta cell function more than glimepiride, both added to metformin, resulting in a superior and longer lasting glycemic and lipid control.

Risk Factors for Coronary Artery Calcifications in Overweight or Obese Persons with Prediabetes: Can They Predict T2 Diabetes and Coronary Vascular Events?

BACKGROUND: It is difficult to predict the risk of developing atherosclerotic cardiovascular disease in subjects with prediabetes and obesity. The aim of this study was to assess risk factors for coronary artery calcifications (CACs) and the development of type 2 diabetes (T2D) and coronary vascular events (CVEs) after 7 years in 100 overweight or obese persons with prediabetes, according to the baseline coronary artery calcium score (CACS). METHODS: Lipids, HbA1c, uric acid, and creatinine were assessed. Glucose, insulin, and c-peptide were determined during an oral glucose tolerance test. Multi-sliced computerized tomography with evaluation of CACS was performed. After 7 years, the subjects were assessed for T2D/CVE. RESULTS: CACs were present in 59 subjects. No single biochemical marker could predict presence of a CAC. After 7 years, T2D developed in 55 subjects (61.8% initially had both IFG and IGT). A gain in weight was the only contributing factor for T2D. Nineteen subjects developed a CVE; increased initial clustering of HOMA-IR > 1.9, LDL > 2.6, and mmol/Land TGL > 1.7 mmol/L and higher CACS were present in that group. CONCLUSIONS: No risk factors for CACs could be identified. A gain in weight is associated with T2D development, as are higher CACS and clustering of high LDL+TGL+HOMA-IR with CVEs.

The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes.

Introduction: A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective: Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods: A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results: Participants were 58.65 ± 7.62 years of age with a body mass index of 35.06 ± 5.15 kg/m², waist circumference of 115.04 ± 15.5 cm, and the duration of diabetes of 4.11 ± 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion: Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.