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.

Early Menopause and Risk of Fractures-A Preventable Gap.

Background: Osteoporosis is a chronic disease that results in microarchitectural changes to the bone, thereby reducing its density and increasing the risk of fractures. This retrospective cross-sectional study aimed to examine the link between the risk of major osteoporotic fractures and hip fractures with the age of menopause onset, as well as the impact of menopause duration on fracture incidence. Methods: This retrospective cross-sectional study was conducted at the Special Hospital for Rheumatic Diseases, Novi Sad, Serbia. The data required for meeting the study objectives were obtained from patients' medical records spanning the 2015-2018 period. The sample for the study comprised of 985 postmenopausal women aged ≥ 50 yr who underwent bone mineral densitometry examination and received a FRAX score for major osteoporotic fractures and hip fractures with and without bone mineral density. The obtained FRAX scores were compared across the subjects with respect to the age of menopause onset and menopause duration. Results: The group that entered into menopause before the age of 45 had a high risk of hip fracture (OR: 1,652; 95% CI: 1,138 - 2,399; P<.01) and a higher mean FRAX score for hip fracture compared to women in whom menopause started after the age of 45 (Me=1.60 vs. 1.30, P<.004). FRAX scores were also correlated with menopause duration, and the difference between the groups with the longest (over 20 yr) and the shortest (1-10 yr) duration was statistically significant at P<.001. Conclusion: As menopause duration could contribute to the prediction of fracture risk, its inclusion in the FRAX algorithm should be considered, while also taking into account the age of menopause onset.

Capture the vertebral fracture: Risk factors as a prediction.

OBJECTIVE: Vertebral fractures are the most common osteoporotic fractures occurring due to low bone mineral density, as well as other risk factors. The aim of the paper is to investigate risk factors for vertebral osteoporotic fracture occurrence in postmenopausal women. METHODS: Retrospective analysis of data pertaining to 651 postmenopausal women obtained from the National Osteoporosis Registry of Serbia was conducted. Further analyses were performed on 217 osteoporotic women identified from those records, whereby those in the experimental group (n= 110) had a vertebral fracture, while those assigned to the control group (n= 107) did not. The two groups were comparable in terms of age (t= 0.450; p> 0.01). Risk factors that could serve as the best predictors of vertebral fracture occurrence were investigated. Multivariate logistic regression analysis was used for testing effect of several factors on vertebral fracture occurrence as the dependent variable. RESULTS: Patients that have never suffered a vertebral fracture had a significantly higher bone mineral density (t= 8.161; p< 0.01) in comparison to those with a verified vertebral fracture. Factors that significantly contributed to the risk of vertebral fracture were presence of kyphosis (OR 708.338; 95% CI 19.238-26.081.950), use of glucocorticoids (OR 87.618; 95% CI 9.175-836.707), and presence of comorbidities (OR 7.327; 95% CI 1.500-35.793). Moreover, a unit increase in body mass index (BMI) was found to lower the probability of vertebral fracture by a factor of 0.846. Women that entered menopause later have lower chance of suffering a vertebral fracture (OR = 0.539; 95% CI 0.400-0.726). CONCLUSION: Lower body mass index, presence of kyphosis, use of glucocorticoids, early menopause onset, and presence of comorbidities are the factors that contribute the most to vertebral osteoporotic fracture occurrence.

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.

[Influence of hormone replacement therapy in postmenopausal women with type 2 diabetes and hyperlipidemia on lipid and glucose metabolism].

INTRODUCTION: Hormone replacement therapy (HRT) is less frequently prescribed to postmenopausal women with diabetes type 2 who have poor lipid status despite well known favorable effect of HRT on lipid levels. OBJECTIVE: The aim of this study was to assess the effect of oral HRT in postmenopausal women with type 2 diabetes and hyperlipidemia. METHOD: Continuously combined HRT, estradiol 2mg + norethisterone acetate 1mg was given to 30 women with diabetes type 2 and hyperlipidemia and two control groups of postmenopausal women (30 with hyperlipidemia only and 30 healthy women) over a 6-month period. Total cholesterol (t-HOL), triglycerides, LDL-cholesterol, HDL-cholesterol, glycosylated hemoglobin A1c (HbA1c) were evaluated in 3-month intervals. Fasting and postprandial glucose levels were evaluated monthly. RESULTS: HRT significantly decreased levels of t-HOL (X2(Friedman) = 11.712; p<0.01) and LDL-c (X2(Friedman) = 10.403; p<0.01) in postmenopausal women with type 2 diabetes. However, the effect was more pronounced in two control groups. Triglycerides (X2(Friedman) = 5.400; p > or = 0.05) and HDL-c (X2(Friedman) = 1.113; p>0.05) did not change in postmenopausal women with type 2 diabetes. Six month of oral HRT significantly decreased HbAlc (F=44.693; p<0.01). Fasting and postprandial glycemia was decreased but not significantly (X2Friedman=6.527; p>0.05). CONCLUSION: Six-month application of HRT is effective in lowering the lipid levels and HbA1c in postmenopausal women with type 2 diabetes. However, target lipid levels were not achieved.