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Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome.
Kaur, V, Dimitriadis, GK, Pérez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, et al
Metabolism: clinical and experimental. 2021;:154908
Abstract
BACKGROUND Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
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2.
Lactobacillus rhamnosus GG and HbA1c in middle age and older adults without type 2 diabetes mellitus: A preliminary randomized study.
Sanborn, VE, Azcarate-Peril, MA, Gunstad, J
Diabetes & metabolic syndrome. 2020;(5):907-909
Abstract
BACKGROUND AND AIMS Probiotic supplementation improves glycemic control in persons with diabetes and the current study examined whether these benefits extend to healthy individuals. METHODS The current study was a 90-day placebo-controlled, double-blind, randomized clinical trial of Lactobacillus rhamnosus GG in healthy middle-aged and older adults. Fasting blood glucose and HbA1c were quantified at baseline and follow up. RESULTS ANCOVA controlling for baseline values showed group differences in follow up HbA1c [F (1,90) = 8.44, p = 0.005]; HbA1c values increased in the placebo group, though remained stable in the probiotic group. CONCLUSIONS If replicated, Lactobacillus rhamnosus GG may protect against changes in glycemic control.
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3.
Effect of oral vitamin D supplementation on glycemic control in patients with type 2 diabetes mellitus with coexisting hypovitaminosis D: A parellel group placebo controlled randomized controlled pilot study.
Upreti, V, Maitri, V, Dhull, P, Handa, A, Prakash, MS, Behl, A
Diabetes & metabolic syndrome. 2018;(4):509-512
Abstract
CONTEXT Vitamin D supplementation in type 2 diabetes mellitus patients may lead to improved glycemic control by improving insulin secretion and decreasing insulin resistance. AIMS To investigate effect of oral vitamin D supplementation on glycemic control, in patients with type 2 diabetes mellitus and coexisting hypovitaminosis D. SETTINGS AND DESIGN Randomized, Parallel Group, Placebo Controlled Trial carried out in a tertiary care hospital of Indian Armed Forces. METHODS AND MATERIAL Sixty patients with coexisting type 2 diabetes mellitus and hypovitaminosis D were randomized into cases and controls and were supplemented with oral Vitamin D and microcrystalline cellulose respectively for six months. Subjects' HbA1c and vitamin D levels were monitored at the beginning and end of the study, fasting plasma glucose (FPG) & post prandial plasma glucose (PPPG) during monthly OPD visits. STATISTICAL ANALYSIS USED Intra-group comparison was made by paired t test & unpaired t test was used for inter-group (A v/s B) comparisons. Repeated measures ANOVA was undertaken to compare values over time. RESULTS The two groups were comparable for all parameters at baseline. Case group showed significant decrease in mean HbA1c levels (7.29% to 7.02%; P = 0.01), mean FPG levels (131.4 to 102.6 mg/dl; P = 0.04) and mean PPPG levels (196.2 to 135.0 mg/dl; P < 0.001). Incidentally, significant improvement in systolic as well as diastolic blood pressure and total cholesterol was also noted in the cases, while for LDL cholesterol improvement tended towards significance (p = 0.05). CONCLUSIONS We found that oral vitamin D supplementation was associated with improved glycemic control and other metabolic parameters in patients with type 2 diabetes mellitus. Supplementation to achieve normal levels of vitamin D can be a promising adjuvant therapy for T2DM patients & coexisting hypovitaminosis D.
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Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients.
Mahmoud, F, Haines, D, Al-Ozairi, E, Dashti, A
Phytotherapy research : PTR. 2016;(3):454-62
Abstract
The present study was undertaken to evaluate the effects of black tea intake on inflammatory cytokines and metabolic biomarkers in Type 2 diabetes mellitus (T2DM). Thirty patients with T2DM were randomly assigned either to a High Intake (HI) group, consuming three cups (600 mL) of black tea per day; and a Low Intake (LI) group, administered 1 cup (200 mL) per day, each during a 12-week period. Intracellular cytokine expression, regulatory T cells (Treg), glycemic and lipid profiles were measured at baseline and following the tea intake period. Tea consumption correlated with major effects measured in peripheral blood of subjects that included significantly reduced glycated hemoglobin (HbA1c) levels, along with increased regulatory T cells CD3+ CD4+ CD25+ FOXP3, CD3+ CD4+ IL-10+ cells (an immunosuppressive phenotype), reduced (pro-inflammatory) CD3+ CD4+ IL-17+ cells and reduced Th1-associated CD3+ CD4+ IFN-Υ+ cells. Tea consumption was also observed to abolish the significance of an inverse correlation between total serum cholesterol and representation of CD4+ IL-4+ T cells, which may reflect protection against atopy-related oxidative stress. Outcomes of this study describe both advantages and limitations to consumption of black tea as an aid to sustained health maintenance by persons at-risk for TD2M and related obesity-associated metabolic syndromes.
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Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance.
Laitinen, T, Lindström, J, Eriksson, J, Ilanne-Parikka, P, Aunola, S, Keinänen-Kiukaanniemi, S, Tuomilehto, J, Uusitupa, M
Diabetic medicine : a journal of the British Diabetic Association. 2011;(6):699-704
Abstract
AIMS: The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort. METHODS Two hundred and sixty-eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow-up, were studied for cardiovascular autonomic neuropathy. At the second annual follow-up visit after the end of lifestyle intervention, we performed deep-breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA(1c,) serum lipids and blood pressure were carried out. RESULTS Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P<0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA(1c) . Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women. CONCLUSIONS Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.
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Retinopathy in subjects with impaired fasting glucose: the NANSY-Eye baseline report.
Tyrberg, M, Melander, A, Lövestam-Adrian, M, Lindblad, U
Diabetes, obesity & metabolism. 2008;(8):646-51
Abstract
AIMS: Network for Pharmacoepidemiology (NEPI) Antidiabetes Study-Eye is a randomized placebo-controlled Swedish trial investigating if treatment with sulphonylurea, in addition to dietary regulation and increased exercise, delays the development of retinopathy in subjects with impaired fasting glucose (IFG). METHODS Subjects were surveyed in primary care with repeated fasting blood glucose measurements. Those with a mean of two consecutive values >or=5.6 and <6.1 mmol/l were invited to participate. Baseline physical examination included blood pressure and body mass index (BMI). Fundus photos were taken in two fields using 35-mm diafilm. The alternative classification of the Wisconsin Epidemiologic Study of Diabetic Retinopathy was used to classify the retinopathy level. RESULTS At baseline, 90 men and 64 women with IFG were photographed. Of these, 16 subjects (10%) had mild or very mild retinopathy. There was no difference in occurrence of retinopathy between subjects with known diagnosis of hypertension or not. However, subjects with retinopathy had significantly higher systolic (154 vs. 141 mmHg, p = 0.013) and diastolic (86 vs. 81 mmHg, p = 0.008) blood pressure levels independent of differences in age, sex and known hypertension. There was a corresponding difference in BMI, being greater in subjects with than in those without retinopathy (32.4 vs. 29.2 kg/m(2), p = 0.013). There were no associations between levels of fasting blood glucose or haemoglobin A1c, on the one hand, and retinopathy, on the other. CONCLUSION Retinopathy may be present even before type 2 diabetes is manifest. It is associated with higher blood pressure levels and higher BMI values, that is, with predominant features of the metabolic syndrome.
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Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.
Bakris, GL, Fonseca, V, Katholi, RE, McGill, JB, Messerli, FH, Phillips, RA, Raskin, P, Wright, JT, Oakes, R, Lukas, MA, et al
JAMA. 2004;(18):2227-36
Abstract
CONTEXT Beta-blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some beta-blockers. OBJECTIVE To compare the effects of beta-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. INTERVENTIONS Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. MAIN OUTCOME MEASURES Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. RESULTS The 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], -0.22% to -0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48); the between-group difference was -7.2% (95% CI, -13.8% to -0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). CONCLUSIONS Both beta-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 beta-blockers on clinical outcomes need to be compared in long-term clinical trials.