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.

Screening for diabetes among Roma people living in Serbia.

AIM: To investigate the prevalence of diabetes in the Roma population in Serbia. METHODS: We screened 11 urban and 8 rural Roma communities from October 2006 to May 2008 for the presence of diabetes. Blood glucose values, name, age, sex, presence of diabetes, family history, and obesity were recorded. RESULTS: We analyzed the data from 1465 Roma people, 953 women and 512 men (785 in urban and 680 in rural communities), with mean age of 42.42-/+15.69 years. Abdominal obesity was present in 600 (41%) participants. Eighty seven participants (5.9%) already had diabetes and there were 76 (5.2%) newly discovered cases of diabetes type 2. Participants with diabetes were significantly older (F=28.33; P<0.01). Family history for diabetes was positive in a third of participants. The risk for diabetes was 3.48 times higher in participants with positive family history (odds ratio [OR], 3.47; 95% confidence interval [CI], 2.37-5.1; P<0.01). Abdominal obesity was less frequent in healthy participants than in participants with diabetes (Chi(2)=32.55; P<0.01). The risk of diabetes in participants with abdominal obesity was 2 times higher than in the non-obese (OR, 2.11; 95% CI, 1.24-3.55; P<0.01). Diabetes was significantly more present in urban communities (Chi(2)=25.20; P<0.01). The risk of developing diabetes was 3.65 times higher in participants from urban settlements (OR, 3.64; 95% CI, 1.99-6.66; P<0.01). CONCLUSION: Prevalence of diabetes in the Roma people living in Serbia may possibly be higher than in the general population of Serbia and needs further investigation.

Unmet Needs in the Management of Type 2 Diabetes Mellitus Patients Starting Insulin Therapy with Basal or Premix Insulin in Routine Clinical Practice in Serbia.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a progressive disease with declining beta cell function, ultimately necessitating insulin therapy. Timely introduction of adequate insulin improves management of diabetes. The aim of this study was to evaluate the unmet needs in the management of T2DM patients recently initiated on insulin therapy in routine clinical practice in Serbia. METHODS: The NEED study was a cross-sectional, observational, multicenter, real-world study conducted in Serbia, involving 26 physicians, endocrinologists, treating individuals with T2DM from 17 secondary health care institutions. Study participants were newly initiated with insulin therapy, being treated with basal or premix insulin ± oral antidiabetics (OAD) for 6-12 months. RESULTS: Four hundred one individuals were included in the study between October 2016 and March 2017. The mean age of study patients was 61.8 ± 9.2 years with mean BMI 30.0 ± 5.0 kg/m2, and duration of diabetes, prior to initiation of insulin therapy, was 8.4 ± 5.9 years. A basal insulin regimen was used by 287 (71.6%) and premix insulin by 114 (28.4%) subjects. The average daily dose (39.8 ± 13.9 units premix vs. 26.3 ± 13.5 units basal), dose/kg (0.47 ± 0.15 units/kg premix vs. 0.31 ± 0.17 units/kg basal), and number of injections per day were higher in the premix compared with basal insulin regimen (p < 0.01). The percentage of T2DM participants with at least one unmet need was high (95.8%). The majority of participants had two or three unmet needs. The most common unmet needs were: HbA1c > 7.0% (79.3%), at least one documented symptomatic hypoglycemia (≤ 3.9 mmol/l) event in the previous 3 months (63.8%), and two or more doses of insulin per day (53.1%). The mean individual HbA1c target was 6.8% in the NEED study cohort, with only 16% of participants reaching it. Most participants [281 (70.1%)] experienced symptomatic hypoglycemia. CONCLUSIONS: The NEED study showed that new insulin users of either basal or premix HM insulin have many unmet needs in the first 6-12 months of treatment. This confirms that in real-life settings novel insulins should be considered in the management of T2DM to reduce the number of symptomatic hypoglycemic events and reach a better HbA1c level. FUNDING: Sanofi, Serbia.

Capture the fracture ­ Use of bone turnover markers in clinical practice.

Bone is a living tissue, metabolically very active, with the level of turnover of about 10% per year. Bone remodeling is a well-balanced process of bone resorption, induced by osteoclasts and bone formationmaintained osteoblasts. Loss of bone remodeling balance, with increased bone resorption, leads to osteoporosis. Bone turnover markers are classified as markers of bone formation and of bone resorption. During the growth and development of skeleton, bone turnover markers show higher levels of activity than in the adult period. The increase in biochemical markers peaks again in the postmenopausal period, indicating accelerated bone remodeling. Bone mineral density is an important predictor of an osteoporotic fracture. Timely assessment of risk factors of osteoporosis and bone markers can detect subjects with accelerated bone remodeling and osteoporosis. This may introduce adequate therapy and prevent fracture.

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.

[Different insulin treatment regimens in patient with diabetes mellitus type 1: effects on quality of life].

BACKGROUND/AIM: Despite of contemporary diabetes mellitus (DM) treatment, one half of patients do not achieve an optimal metabolic control. Considering great psychological burden of diabetic patients, the purpose of this study was to assess the effect of different insulin treatment regimens, glycemic control and the presence of vascular complications on self-reported well-being and quality of life (QoL) of subjects with type 1 DM. METHODS: The patients with type 1 DM (n=122) recruited from the outpatient Diabetes Endocrinology Clinic of Zvezdara University Medical Center were divided into 4 groups according to the specific treatment regimen: 26 were on continuous subcutaneous insulin infusion (CSII), 30 on conventional insulin therapy, 33 on multiple daily injections (MDI) with human insulins, and 33 on MDI with insulin analogues. QoL was assesed by self-reported well-being with the following questionnaires: WHO-5 item well being index (WHO-5), 36 item short form (SF-36) survey, and insulin treatment appraisal scale (ITAS). Objective metabolic control was assessed by glycosylated hemoglobin (HbA1c), lipid levels and the presence of vascular complications. Statistical analyses used in this cross-sectional study included: descriptive statistics, student's t-test, chi-sqare test, contingency tables, ANOVA and correlation methods. RESULTS: The patients on CSII had significantly better metabolic control than all other treatment groups, especially when compared to the one on conventional therapy (CSII HbA1c 7.07 +/- 1.48% vs. conventional therapy, HbA1c 10.04 +/- 1.44; p = 0.000). No significant difference in glycemic control was observed between patients on MDI with human insulins and insulin analogues. Good glycemic control significantly influenced the reported QoL. The patients with retinopathy and nephropathy reported significantly lower physical well-being, and the patients with polyneuropathy and cardiovascular complications reported also lower psychological well being. CONCLUSIONS: Insulin treatment regiment selection affects not only objective metabolic control, but also QoL.

[The effects of metformin plus sulfonylurea therapy on clinical features of the metabolic syndrome].

INTRODUCTION: Insulin resistance is a well-known leading factor in the development of metabolic syndrome. The aim of this study was to evaluate metabolic effects of metformin added to sulfonylurea in unsuccessfully treated type 2 diabetic patients with metabolic syndrome. MATERIAL AND METHODS: A group of thirty subjects, with type 2 diabetes, secondary sulfonylurea failure and metabolic syndrome were administered the combined therapy of sulfonylurea plus metformin for six months. Metformin 2000 mg/d was added to previously used sulfonylurea agent in maximum daily dose. Antihypertensive and hypolipemic therapy was not changed. The following parameters were assessed at the beginning and after six months of therapy: glycemic control, body mass index, waist circumference, blood pressure, triglycerides, total cholesterol and its fractions, homeostatic models for evaluation of insulin resistance and secretion (HOMA R, HOMA B) and C- peptide. RESULTS: Glycemic control was significantly improved after six months of the combined therapy: (fasting 789 vs. 10.61 mmol/l. p < 0.01; postprandial 11.12 vs. 12.61 mmol/l. p < 0.01, p < 0.01; glycosylated hemoglobin 6.81 is. 8.83%. p < 0.01) the body mass index and waist circumference were significantly lower (26.7 vs. 27.8 kg/m2, p < 0.01 and 99.7 vs. 101.4 cm for men, p < 0.01, 87.2 vs. 88.5 for women, p < 0.01). Fasting plasma triglycerides decreased from 3.37 to 2.45 mmol/l (p < 0.01) and HOMA R from 7.04 to 5.23 (p < 0.001). No treatment effects were observed on blood pressure, cholesterol, and residual insulin secretion. CONCLUSION: Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.

[Role of standard test meal in initiation of insulin therapy in type 2 diabetes].

INTRODUCTION: Secondary monotherapy failure in diabetes mellitus type 2 occurs early in the course of disease. Choosing the optimal combination therapy depends on the primary pathogenic mechanism. Evaluation of the residual beta cell function is of primary importance in deciding whether insulin should be included in the combination therapy. OBJECTIVE: To investigate the influence of standard meal test and homeostasis model assessment (HOMA-B) index, as markers of residual insulin secretion, on the efficacy of two different therapeutic strategies in secondary sulphonylurea (SU) failure. METHODS: In the group of thirty subjects with diabetes type 2, metabolic syndrome and secondary SU failure, metformin (MET) was added for the following six months. In the group of 30 subjects with diabetes type 2, secondary SU failure, with no metabolic syndrome, insulin (INS) was added for the same period. During the six-month follow-up period, fasting, postprandial, mean daily blood glucose and glycosylated haemoglobin (HbA1C) were evaluated. Fasting and meal stimulated C-peptide (CP) and insulin levels were measured at the beginning; absolute and relative increase of CP (delta CP, delta CP%), and HOMA-B were calculated. Correlation between CP secretion and HOMA-B at the beginning and glycaemic control after six months of therapy were evaluated by using Pearson correlation coefficient. RESULTS: Glycaemic control after six months was significantly improved in both therapeutic combinations (p < 0.01). However, target values were not met in either group. Stimulated CP levels correlated best with all the parameters of glycaemic control in the group SU+MET (r -0.479 to -0.791; p < 0.01), and in the group SU+INS (r 0.382 to 0.635; p < 0.01). HOMA-B correlated only with HbA1C in the SU+MET group (r = -0.382; p < 0.05). CONCLUSION: Clinical diagnosis of metabolic syndrome and evaluation of residual insulin secretion are necessary in choosing the best combination therapy in secondary SU failure in subjects with type 2 diabetes. Stimulated standard meal CP level is a clinically useful marker of residual insulin secretion.