Screening, prevalence, treatment and control of kidney disease in patients with type 1 and type 2 diabetes in low-to-middle-income countries (2005-2017): the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: Diabetes is the leading cause of kidney disease worldwide. There is limited information on screening, treatment and control of kidney disease in patients with diabetes in low-to-middle-income countries (LMICs). METHODS: The International Diabetes Management Practices Study is an ongoing, non-interventional study of clinical profiles and practices among patients receiving outpatient care mainly by internal medicine physicians and endocrinologists in LMICs. We examined screening, prevalence, treatment and control of kidney disease across seven waves (W) of data collection between 2005 and 2017. RESULTS: Among 15,079 patients with type 1 and 66,088 patients with type 2 diabetes, screening for kidney disease increased between W2 and W3 followed by a plateau (type 1 diabetes: W2, 73.7%; W3, 84.1%; W7, 83.4%; type 2 diabetes: W2, 65.1%; W3, 82.6%; W7, 86.2%). There were also decreasing proportions of patients with microalbuminuria (type 1 diabetes: W1, 27.1%; W3, 14.7%; W7, 13.8%; type 2 diabetes: W1, 24.5%; W3, 12.6%; W7, 11.9%) and proteinuria (type 1 diabetes: W1, 14.2%; W3, 8.7%; W7, 8.2%; type 2 diabetes: W1, 15.6%; W3, 9.3%; W7, 7.6%). Fewer patients were reported as receiving dialysis for both type 1 diabetes (W2, 1.4%; W7, 0.3%) and type 2 diabetes (W2, 0.9%; W7, 0.2%) over time. While there was no change in mean HbA1c or prevalence of diagnosed hypertension (type 1 diabetes: W1, 22.7%; W7, 19.9%; type 2 diabetes: W1, 60.9%; W7, 66.2%), the use of statins had increased among patients diagnosed with dyslipidaemia (type 1 diabetes: W1, 77.7%; W7, 90.7%; type 2 diabetes: W1, 78.6%; W7, 94.7%). Angiotensin II receptor blockers (type 1 diabetes: W1, 18.0%; W7, 30.6%; type 2 diabetes: W1, 24.2%; W7, 43.6%) were increasingly used over ACE inhibitors after W1 (type 1 diabetes: W1, 65.0%; W7, 55.9%; type 2 diabetes: W1, 55.7%, W7, 41.1%) among patients diagnosed with hypertension. CONCLUSIONS/INTERPRETATION: In LMICs, real-world data suggest improvement in screening and treatment for kidney disease in patients with type 1 and type 2 diabetes attending non-nephrology clinics. This was accompanied by decreasing proportions of patients with microalbuminuria and proteinuria, with fewer patients who reported receiving dialysis over a 12-year period.

Correction to: Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12 years of real-world evidence of the International Diabetes Management Practices Study (IDMPS).

Unfortunately, the standard deviations for 'last HbA1c measurement' in mmol/mol were miscalculated in Table 1 of this paper.

Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12 years of real-world evidence of the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: We evaluated the secular trend of glycaemic control in individuals with type 2 diabetes in developing countries, where data are limited. METHODS: The International Diabetes Management Practices Study provides real-world evidence of patient profiles and diabetes care practices in developing countries in seven cross-sectional waves (2005-2017). At each wave, each physician collected data from ten consecutive participants with type 2 diabetes during a 2 week period. The primary objective of this analysis was to evaluate trends of glycaemic control over time. RESULTS: A total of 66,088 individuals with type 2 diabetes were recruited by 6099 physicians from 49 countries. The proportion of participants with HbA1c <53 mmol/mol (<7%) decreased from 36% in wave 1 (2005) to 30.1% in wave 7 (2017) (p < 0.0001). Compared with wave 1, the adjusted ORs of attaining HbA1c ≤64 mmol/mol (≤8%) decreased significantly in waves 2, 5, 6 and 7 (p < 0.05). Over 80% of participants received oral glucose-lowering drugs, with declining use of sulfonylureas. Insulin use increased from 32.8% (wave 1) to 41.2% (wave 7) (p < 0.0001). The corresponding time to insulin initiation (mean ± SD) changed from 8.4 ± 6.9 in wave 1 to 8.3 ± 6.6 years in wave 7, while daily insulin dosage ranged from 0.39 ± 0.21 U/kg (wave 1) to 0.33 ± 0.19 U/kg (wave 7) for basal regimen and 0.70 ± 0.34 U/kg (wave 1) to 0.77 ± 0.33 (wave 7) U/kg for basal-bolus regimen. An increasing proportion of participants had ≥2 HbA1c measurements within 12 months of enrolment (from 61.8% to 92.9%), and the proportion of participants receiving diabetes education (mainly delivered by physicians) also increased from 59.0% to 78.3%. CONCLUSIONS: In developing countries, glycaemic control in individuals with type 2 diabetes remained suboptimal over a 12 year period, indicating a need for system changes and better organisation of care to improve self-management and attainment of treatment goals.

Does treatment with sodium-glucose co-transporter-2 inhibitors have an effect on sleep quality, quality of life, and anxiety levels in people with Type 2 diabetes mellitus?

Background/aim: To evaluate the impact of treatment with sodium-glucose co-transporter-2 (SGLT2) Inhibitors on quality of life (QoL), sleep quality (SQ), and anxiety levels in patients with Type 2 diabetes mellitus (T2DM). Materials and methods: Ninety-seven patients with type 2 diabetes admitted to tertiary care hospital diabetes clinic were included. Fifty patients were randomized to receive SGLT2 inhibitors in addition to baseline treatment (Group A), 47 subjects continued with their baseline treatment or were added other medications as needed (Group B). Thirty healthy controls (HC) were recruited (Group C). All groups were subjected to the Turkish version of Short Form-36 (SF-36), Pittsburgh Sleep Quality (PSQ), and Beck Anxiety Inventory (BAI) scales both at baseline and final visit. Results: Physical function, emotional role limitation, vitality, mental health, pain, general health perception scores of SF-36 were significantly improved in Group A, at the end of the follow-up period. There was no significant change in terms of PSQ, BAI scores, and hypoglycaemia documented in all groups. The intervention-related change in HbA1c level, body weight, and body mass index were significantly higher in Group A. Conclusion: The QoL was improved in people with diabetes who were taking SGLT2 inhibitors. This may be explained by weight loss observed in participants.

Patient-reported outcomes and treatment adherence in type 2 diabetes using natural language processing: Wave 8 of the Observational International Diabetes Management Practices Study.

AIMS/INTRODUCTION: We analyzed patient-reported outcomes of people with type 2 diabetes to better understand perceptions and experiences contributing to treatment adherence. MATERIALS AND METHODS: In the ongoing International Diabetes Management Practices Study, we collected patient-reported outcomes data from structured questionnaires (chronic treatment acceptance questionnaire and Diabetes Self-Management Questionnaire) and free-text answers to open-ended questions to assess perceptions of treatment value and side-effects, as well as barriers to, and enablers for, adherence and self-management. Free-text answers were analyzed by natural language processing. RESULTS: In 2018-2020, we recruited 2,475 patients with type 2 diabetes (43.3% insulin-treated, glycated hemoglobin (HbA1c) 8.0 ± 1.8%; 30.9% with HbA1c <7%) from 13 countries across Africa, the Middle East, Europe, Latin America and Asia. Mean ± standard deviation scores of chronic treatment acceptance questionnaire (acceptance of medication, rated out of 100) and Diabetes Self-Management Questionnaire (self-management, rated out of 10) were 87.8 ± 24.5 and 3.3 ± 0.9, respectively. Based on free-text analysis and coded responses, one in three patients reported treatment non-adherence. Overall, although most patients accepted treatment values and side-effects, self-management was suboptimal. Treatment duration, regimen complexity and disruption of daily routines were major barriers to adherence, whereas habit formation was a key enabler. Treatment-adherent patients were older (60 ± 11.6 vs 55 ± 11.7 years, P < 0.001), and more likely to have longer disease duration (12 ± 8.6 vs 10 ± 7.7 years, P < 0.001), exposure to diabetes education (73.1% vs 67.8%, P < 0.05), lower HbA1c (7.9 ± 1.8% vs 8.3 ± 1.9%, P < 0.001) and attainment of HbA1c <7% (29.7% vs 23.3%, P < 0.01). CONCLUSIONS: Patient perceptions/experiences influence treatment adherence and self-management. Patient-centered education and support programs that consider patient-reported outcomes aimed at promoting empowerment and developing new routines might improve glycemic control.

Effect of nateglinide on the incidence of diabetes and cardiovascular events.

BACKGROUND: The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS: In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)

Effect of valsartan on the incidence of diabetes and cardiovascular events.

BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)

Status of Weight Change, Lifestyle Behaviors, Depression, Anxiety, and Diabetes Mellitus in a Cohort with Obesity during the COVID-19 Lockdown: Turk-Com Study Group.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to a lockdown period. Confinement periods have been related to unhealthy lifestyle behaviors. Our study aimed to determine weight change, changes in eating and exercise habits, the presence of depression and anxiety, and diabetes mellitus (DM) status in a cohort of patients with obesity. METHODS: The study was undertaken in nine centers of Collaborative Obesity Management (COM) of the European Association for the Study of Obesity (EASO) in Turkey. An e-survey about weight change, eating habits, physical activity status, DM status, depression, and anxiety was completed by patients. The International Physical Activity Questionnaire (IPAQ) score was used to determine physical activity in terms of metabolic equivalents (METs). A healthy nutrition coefficient was calculated from the different categories of food consumption. The Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7) Questionnaire  were used for determining depression and anxiety, respectively. RESULTS: Four hundred twenty-two patients (age 45 ± 12.7 years, W/M = 350/72) were included. The healthy nutrition coefficient before the pandemic was 38.9 ± 6.2 and decreased to 38.1 ± 6.4 during the pandemic (p < 0.001). Two hundred twenty-nine (54.8%) patients gained weight, 54 (12.9%) were weight neutral, and 135 (32.3%) lost weight. Patients in the weight loss group had higher MET scores and higher healthy nutrition coefficients compared with the weight gain and weight-neutral groups (p < 0.001). The PHQ and GAD scores were not different between the groups. Percent weight loss was related to healthy nutrition coefficient (CI: 0.884 [0.821-0.951], p = 0.001) and MET categories (CI: 0.408 [0.222-0.748], p = 0.004). One hundred seventy patients had DM. Considering glycemic control, only 12 (8.4%) had fasting blood glucose <100 mg/dL and 36 (25.2%) had postprandial BG <160 mg/dL. When patients with and without DM were compared in terms of dietary compliance, MET category, weight loss status, PHQ-9 scores, and GAD-7 scores, only MET categories were different; 29 (11.7%) of patients in the nondiabetic group were in the highly active group compared with 5 (2.9%) in the diabetic group. CONCLUSION: The COVID-19 lockdown resulted in weight gain in about half of our patients, which was related to changes in physical activity and eating habits. Patients with DM who had moderate glycemic control were similar to the general population in terms of weight loss but were less active.

Expert Panel Recommendations for Use of Standardized Glucose Reporting System Based on Standardized Glucometrics Plus Visual Ambulatory Glucose Profile (AGP) Data in Clinical Practice.

This expert panel of diabetes specialists aimed to provide guidance to healthcare providers on the best practice in the use of innovative continuous glucose monitoring (CGM) techniques through a practical and implementable document that specifically addresses the rationale for and also analysis and interpretation of the new standardized glucose reporting system based on standardized CGM metrics and visual ambulatory glucose profile (AGP) data. This guidance document presents recommendations and a useful algorithm for the use of a standardized glucose reporting system in the routine diabetes care setting.

One in Seven Insulin-Treated Patients in Developing Countries Reported Poor Persistence with Insulin Therapy: Real World Evidence from the Cross-Sectional International Diabetes Management Practices Study (IDMPS).

INTRODUCTION: Although poor adherence to insulin is widely recognised, periodic discontinuation of insulin may cause more severe hyperglycaemia than poor adherence. We assessed persistence with insulin therapy in patients with type 1 (T1D) or type 2 diabetes (T2D) in developing countries and the reasons for insulin discontinuation. METHODS: The International Diabetes Management Practices Study collected real-world data from developing countries in seven waves between 2005 and 2017. In Wave 7 (2016-2017), we asked adult patients with T1D and insulin-treated T2D to report whether they had ever discontinued insulin, the estimated duration of discontinuation and underlying reasons. RESULTS: Among 8303 patients recruited from 24 countries by 620 physicians, 4596 were insulin-treated (T1D: 2000; T2D: 2596). In patients with T1D, 14.0% (95% CI: 12.5-15.6) reported having self-discontinued insulin for a median duration of 1.0 month (IQR: 0.5, 3.5). The respective figures in patients with T2D were 13.7% (12.4-15.1) and 2.0 months (IQR: 1.0, 6.0). The main reasons for discontinuation were impact on social life (T1D: 41.0%; T2D: 30.5%), cost of medications and test strips (T1D: 34.4%; T2D: 24.5%), fear of hypoglycaemia (T1D: 26.7%; T2D: 28.0%) and lack of support (T1D: 26.4%; T2D: 25.9%). Other factors included age < 40 years, non-university education and short disease duration (T1D: ≤ 1 year; T2D: > 1-≤ 5 years). Patients with T1D who did not perform self-monitoring of blood glucose (SMBG) or self-adjust their insulin dosage, and patients with T1D or T2D without glucose meters were less likely to persist with insulin. Nearly 50% of patients who reported poor persistence had HbA1c > 75 mmol/mol (> 9%) and > 50% of physicians recommended diabetes education programmes to improve treatment persistence. CONCLUSION: In developing countries, poor persistence with insulin is common among insulin-treated patients, supporting calls for urgent actions to ensure easy access to insulin, tools for SMBG and education.

High Prevalence of Depressive Symptoms in Patients With Type 1 and Type 2 Diabetes in Developing Countries: Results From the International Diabetes Management Practices Study.

OBJECTIVE: Depression is common in people with diabetes, but data from developing countries are scarce. We evaluated the prevalence and risk factors for depressive symptoms in patients with diabetes using data from the International Diabetes Management Practices Study (IDMPS). RESEARCH DESIGN AND METHODS: IDMPS is an ongoing multinational, cross-sectional study investigating quality of care in patients with diabetes in real-world settings. Data from wave 5 (2011), including 21 countries, were analyzed using the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Logistic regression analyses were conducted to identify risk factors of depressive symptoms. RESULTS: Of 9,865 patients eligible for analysis, 2,280 had type 1 and 7,585 had type 2 diabetes (treatment: oral glucose-lowering drugs [OGLD] only, n = 4,729; OGLDs plus insulin, n = 1,892; insulin only, n = 964). Depressive symptoms (PHQ-9 score ≥5) were reported in 30.7% of those with type 1 diabetes. In patients with type 2 diabetes, the respective figures were 29.0% for OGLDs-only, 36.6% for OGLDs-plus-insulin, and 46.7% for insulin-only subgroups. Moderate depressive symptoms (PHQ-9 score 10-19) were observed in 8-16% of patients with type 1 or type 2 diabetes. Female sex, complications, and low socioeconomic status were independently associated with depressive symptoms. In type 1 diabetes and in the type 2 diabetes OGLDs-only group, depression was associated with poor glycemic control. CONCLUSIONS: Depressive symptoms are common in patients with diabetes from developing countries, calling for routine screening, especially in high-risk groups, to reduce the double burden of diabetes and depression and their negative interaction.

The Role of Obesity in Predicting the Clinical Outcomes of COVID-19.

INTRODUCTION: The aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19. METHODS: We included the patients >18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight <25 kg/m2 (Group A), overweight from 25 to <30 kg/m2 (Group B), Class I obesity 30 to <35 kg/m2 (Group C), and ≥35 kg/m2 (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups. RESULTS: There was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [p = 0.017], Group D vs. Group A [p = 0.001], and Group D vs. Group C [p = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [p = 0.025], Group D vs. Group A [p < 0.001], Group D vs. Group B [p = 0.006], and Group D vs. Group C [p = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [p < 0.001], Group C vs. Group A [p < 0.001], Group D vs. Group A [p < 0.001], Group D vs. Group B [p < 0.001], and Group D vs. Group C [p = 0.010]). CONCLUSION: COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications.

Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries.

BACKGROUND: Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically. AIMS: To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries. METHODS: We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data. RESULTS: Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients. CONCLUSIONS: Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes.

Serum levels of p53 and cytochrome c in subjects with type 2 diabetes and impaired glucose tolerance.

PURPOSE: To examine apoptotic markers in serum of subjects with diabetes and impaired glucose tolerance (IGT). Serum levels of p53 and cytochrome c, regulator molecules for apoptosis, were measured in subjects with type 2 diabetes, subjects with IGT and healthy controls. METHODS: Forty one subjects with type 2 diabetes, 27 with IGT and 27 healthy volunteers were included in the study. Serum level of cytochrome c and p53 were measured with competitive ELISA. RESULTS: Serum levels of p53 were lower in the group of subjects with type 2 diabetes (085+/-0.39 U/ml) than in controls (1.09+/-0.49 U/ml) (P < 0.05) and in the subjects with IGT (0.98+/-0.37 U/ml) (P < 0.05). There was no significant difference between the group with IGT and controls. Also, there was no difference for serum level of cytochrome c among the groups. In the group of subjects with type 2 diabetes, serum level of cytochrome c was mildly correlated with HbA1c (r:0.39, P < 0.05). CONCLUSION: The present study shows that the serum level of p53 is lower in the patients with type 2 diabetes than in controls or in subjects with IGT. No difference was seen among the the groups for the serum level of cytochrome c.

Diabetes education and health insurance: How they affect the quality of care provided to people with type 1 diabetes in Latin America. Data from the International Diabetes Mellitus Practices Study (IDMPS).

AIMS: This study aimed to evaluate the impact of diabetes education and access to healthcare coverage on disease management and outcomes in Latin America. METHODS: Data were obtained from a sub-analysis of 2693 patients with type 1 diabetes mellitus recruited from 9 Latin American countries as part of the International Diabetes Mellitus Practices Study (IDMPS), a multinational, observational survey of diabetes treatment in developing regions. RESULTS: Results from the Latin American cohort show that only 25% of participants met HbA1c target value (< 7% [53 mmol/mol]). Attainment of this target was significantly higher among participants who had received diabetes education than those who hadn't (28% vs. 19%, p < 0.001), and among those who practiced self-management (27% vs. 21% no self-management, p = 0.001). Multivariate analysis showed that participants who had received diabetes education were more likely to manage their diabetes (OR:1.65 [95% CI: 1.24, 2.19]; p = 0.001), and to attain HbA1c target values (OR:1.48 [95% CI: 1.14, 1.93]; p = 0.003). CONCLUSIONS: Given the association between uncontrolled diabetes and long-term complications, health authorities and care providers should increase efforts to ensure widespread healthcare coverage and access to self-management education to reduce the socioeconomic and humanistic burden of type 1 diabetes.

Orlistat augments postprandial increases in glucagon-like peptide 1 in obese type 2 diabetic patients.

OBJECTIVE: Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 29 type 2 diabetic patients, who were not taking insulin or alpha-glucosidase inhibitors, were enrolled in the study. On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules, followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose. RESULTS: All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides. CONCLUSIONS: The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug.

Effect of oxidative stress on glutathione pathway in red blood cells from patients with insulin-dependent diabetes mellitus.

Recently, increased oxidative stress and impaired antioxidant defense have been suggested as a contributory factor for initiation and progression of complications in diabetes. Although glutathione (GSH) and the enzymes included by glutathione redox cycle have an important role for protection of cells against free radical-mediated damage, they may be susceptible to oxidation themselves. We examined the susceptibility of the GSH pathway to oxidation and inactivation in subjects with well-controlled and poorly controlled insulin-dependent diabetes mellitus (IDDM) versus controls and the effect of glycemic control on this susceptibility. Red blood cells (RBCs) were isolated, RBC level of GSH, activity of glutathione peroxidase (G-Px), and glutathione reductase (G-Red) were measured at the baseline and after a 2-hour incubation with hydrogen peroxide. Significant decreases were observed in the GSH level and in the activity of GSH peroxidase and GSH reductase in all the groups after the incubation with hydrogen peroxide. Maximum decrease was observed in the poorly controlled diabetic group for all parameters. This result indicates that the GSH pathway is susceptible to oxidation; and this susceptibility increases in poorly controlled diabetics. Therefore, insufficient antioxidant defense by the GSH pathway may be one of the factors responsible for development of complications in patients with IDDM.

Susceptibility of glutatione and glutathione-related antioxidant activity to hydrogen peroxide in patients with type 2 diabetes: effect of glycemic control.

OBJECTIVES: The aim of the present study was to examine the susceptibility of glutathione (GSH) and glutathione related antioxidant enzymes to oxidation in type 2 diabetic patients with and without glycemic control. DESIGN AND METHODS: Erythrocyte glutathione level and activities of glutathione peroxidase (G-Px), glutathione reductase (G-Red) and glutathione S-transferase (GST) in controls, well controlled and poorly controlled type 2 diabetics were measured by spectrophotometric assays before and after the incubation in vitro with H2O2. RESULTS: GSH level, G-Px and G-Red activities decreased but GST activity increased in the erythrocytes from all the groups after the incubation with H2O2. Percentage of decrease in GSH was independent from glycemic control, whereas the percentage of decreases in G-Px and G-Red was related to glycemic control. The percentage of increase in GST was found to be independent from diabetes. CONCLUSIONS: GSH and GSH-related antioxidant enzymes in human erythrocytes are susceptible to oxidation, particularly, G-Px and G-Red which were found to be more susceptible to oxidation in erythrocytes from poorly controlled type 2 diabetic patients.

O(6)-methylguanine DNA methyltransferase activity in diabetic patients.

In the present study, we evaluated O(6)-methylguanine-DNA methyltransferase (MGMT) activity in diabetic patients. The study was performed on 27 patients with Type 1 diabetes, and 42 with Type 2 diabetes. Patients with complications were excluded from the study. 36 non-diabetic volunteers, non-smokers who do not consume alcoholic beverage, were chosen from the medical staff as control subjects. MGMT activity was measured by the transfer of radiolabeled methyl groups from a prepared methylguanine-DNA substrate to the enzyme fraction of leukocyte extract. Leukocyte MGMT activity was significantly reduced in both Type 1 and Type 2 diabetes patients as compared with control subjects (P<0.001). The present study demonstrates decreased MGMT activity in leukocytes from patients with Type 1 and Type 2 diabetes.

Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes.

The first aim of the present study was to examine the relationship between reduced glutathione (GSH) level, a powerful cellular antioxidant, and oxidative damage to DNA; and secondly, to see the effect of glycemic control on oxidative DNA damage in type 2 diabetics. We determined GSH level and, using the comet assay, formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites which indicates oxidised guanine in freshly isolated blood from age-matched type 2 diabetics and controls. We found significant differences between men and women in the control group for both GSH and Fpg-sensitive sites. Therefore, we compared the controls and type 2 diabetics separately in men and women. GSH level of whole blood was found to be lower, Fpg-sensitive sites in leukocytes was found to be higher in the both type 2 diabetic men and women, as compared with their respective controls. When the diabetic group was divided into two groups as well-controlled diabetics and poorly-controlled diabetics with respect to glycosylated haemoglobine levels, it was found that Fpg-sensitive sites was significantly higher in the poorly-controlled diabetics than in the well-controlled diabetics in both the men and women. GSH level was lower in the poorly-controlled diabetics but not significantly. Fpg-sensitive sites were found to be moderately correlated with both glycosylated haemoglobine and GSH, and weakly correlated with glucose. Data indicate that decreased GSH level may be a contributory factor for enhanced oxidative DNA damage in type 2 diabetics; and chronic hyperglycemia derived from poorly-controlled diabetic conditions may induce oxidative DNA damage in these patients.