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The Khatri Sikh Diabetes Study (SDS): study design, methodology, sample collection, and initial results.

Non-insulin-dependent diabetes mellitus, or type 2 diabetes (T2DM), has become a major public health problem in India. The high prevalence, relatively young age of onset, and strong familial aggregation of T2DM in some Indian communities remains to be explained. Many of the traditional risk factors established for European populations do not appear to be present in Asian Indians. Phase I of the Sikh Diabetes Study (SDS) was launched to build the population resources required to initiate a large-scale genetic epidemiological study of diabetes in an Asian Indian population. The SDS is focused on the Khatri Sikh population of North India. In all, 1,892 subjects were enrolled to participate in the family-based study; 1,623 of these subjects belong to 324 families, each of which has at least 2 siblings affected with T2DM. The sample included 1,288 individuals affected with T2DM (siblings, parents, or relatives) and 335 unaffected siblings, parents, or relatives. The remaining 269 subjects were unrelated nondiabetic control subjects, including unaffected spouses of probands or siblings. This primarily nonvegetarian, nonsmoking endogamous caste group has presented an unusual clinical picture of uneven distribution of adiposity and a high rate of T2DM with secondary complications. Such well-characterized population isolates may offer unique advantages in mapping genes for common complex diseases.

Adult↗

Cost-effectiveness and budget impact of obesity surgery in patients with type-2 diabetes in three European countries.

BACKGROUND: We aimed to establish a payer-perspective cost-effectiveness and budget impact (BI) model of adjustable gastric banding (AGB) and gastric bypass (GBP) vs conventional treatment (CT) in patients with BMI > or =35 kg/m(2) and type-2 diabetes T2DM, in Germany, UK and France. METHODS: Clinical evidence was obtained from literature and patient-reported EQ-5D scores given BMI and T2DM status from HODaR. Resource utilization data in AGB, GBP and CT were obtained from quoted publications so as to reflect practice in 2005. CT in each country was based on descriptions in HTA reports or based on co-authors' experience of current practice. Unit costs were obtained from published sources when available, or from co-authors' institutions. A deterministic algorithm with cost and utility discounting, enabled selection of inputs independently throughout the time scope for each of the 3 treatments, and included mean BMI, amounts of resources and unit costs. RESULTS: The base case time-scope was 5 years, and the annual discount rate for utilities and costs was 3.5%. Compared to CT, GBP yielded +80.8 kg/m(2).years, +2.6 T2DM-free-years and +1.34 QALYs. AGB yielded +57.8 kg/m(2).years, +2.5 T2DM-free-years and +1.03 QALYs. In Germany and France, both GBP and AGB yielded a cost decrease, and were thus dominant in terms of ICER compared to CT. In the UK, GBP and AGB yielded a cost increase, but were cost-effective. CONCLUSION: In patients with T2DM and BMI > or =35 kg/m(2), AGB and GBP are effective at 5-year follow-up in cost-saving in Germany and France, and are cost-effective in the UK with a moderate BI vs CT.

Body Mass Index↗

Diabetes and periodontal disease: a case-control study.

BACKGROUND: Periodontitis is often associated with diabetes and might be considered one of the chronic complications of diabetes mellitus, both in Type 1 (T1DM) and Type 2 (T2DM). This case-control study was designed to evaluate the possible association between non-insulin-dependent diabetes (T2DM) and clinical and microbiological periodontal disease among adult Sardinians. METHODS: A total of 212 individuals participated in this study: 71 T2DM patients aged 61.0 +/- 11.0 years and 141 non-diabetic controls in good general health aged 59.1 +/- 9.2 years. All subjects were given a clinical periodontal examination for probing depth, attachment level, presence of calculus, bleeding on probing, and assessment of plaque. Subgingival plaque samples were obtained, and P. gingivalis, P. intermedia, and T. forsythensis were identified using multiplex polymerase chain reaction. RESULTS: T2DM patients showed a significantly lower number of teeth present (P = 0.002); a significant increase in number of probing depths >4 mm, and percent of pocket depths >4 mm (P = 0.04 and P = 0.05, respectively); periodontitis (P = 0.046); bleeding on probing (P = 0.02); and plaque index (P = 0.01). A significant association with diabetes was detected for plaque (X2= 4.46; P <0.05) and bleeding on probing (X2= 3.60; P <0.05). Concerning bacteria prevalence, a positive association was detected for P. gingivalis (X2= 2.80; P <0.05) and T. forsythensis (X2= 3.87; P <0.05). Presence of plaque was positively associated with case status (odds ratio [OR] = 1.3; 95% confidence interval [CI]: 1.2, 3.6) and with prevalence of P. gingivalis and T. forsythensis (OR = 1.2, 95% CI: 1.3, 2.2; and 1.2, 95% CI: 1.2, 1.8, respectively). CONCLUSION: Patients with T2DM undoubtedly have a susceptibility for more severe periodontal disease.

Adult↗

Exploring the Potential Molecular Targets of Cyanidin-3-O-glucoside for Type 2 Diabetes Mellitus Treatment.

INTRODUCTION: This study aims to elucidate the multi-target molecular mechanism of cyanidin-3-O-glucoside (C3G) in treating Type 2 Diabetes (T2DM) through network pharmacology methods. METHODS: The study was designed to predict the targets of C3G through public databases and to screen for T2DM-related targets. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the common targets. Core targets were further validated through molecular docking and molecular dynamics (MD) simulations. RESULTS: This research identified a total of 57 potential targets of C3G in the treatment of T2DM. Subsequent PPI analysis identified ALB (Degree=43), AKT1 (Degree=41), and TNF (Degree=41) as the top three hub proteins. Pathway analysis indicated significant involvement in the insulin signaling pathway (P = 4.205&#xd7;10-9), AMPK signaling pathway (P = 9.582&#xd7;10-7), and FoxO signaling pathway (P = 1.315&#xd7;10-6). Molecular docking revealed strong binding affinities between C3G and NOS3 (-9.5 kcal/mol), PPARG (-9.0 kcal/mol), TNF (-8.5 kcal/mol), and INSR (-8.4 kcal/mol). MD simulations further confirmed that the C3G-target complex has excellent binding stability. DISCUSSION: C3G may intervene in the pathological progression of T2DM by regulating key pathways such as insulin sensitivity, inflammatory responses, and oxidative stress. Further studies suggest that INSR and NOS3 may be new targets through which C3G exerts its effects, but their specific mechanisms and in vivo biological functions still need to be elucidated by subsequent experiments. CONCLUSION: C3G may intervene in the progression of T2DM in a multi-pathway synergistic manner by targeting key molecules such as INSR and NOS3.

Anthocyanins↗

Prevention of type 2 diabetes.

Changes in the human environment and in human behavior and lifestyle, in conjunction with genetic susceptibility, have resulted in a dramatic increase in the incidence and prevalence of diabetes in the world. The rapid escalation of the number of people with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease demands urgent action on prevention. The Finnish Diabetes Prevention Study and The Diabetes Prevention Program showed that the prevention (or delaying) of T2DM is feasible and effective. Both of these trials led to a reduction of 58% in the conversion to diabetes in subjects with impaired glucose tolerance. Compared to lifestyle changes, drug treatment in the prevention of diabetes in people at high risk for T2DM has been less beneficial. Metformin (31%) or acarbose (25%) treatment obtained only about a half of the reduction in the conversion to diabetes compared to lifestyle changes. These drugs require monitoring, and have significant side-effects. Also the effect of orlistat (37%) did not reach the effect of lifestyle modification. Results of the Troglitazone in Prevention of Diabetes study are suggestive for the prevention, but the trial was too small, and included only one ethnic group (Hispanic) and one gender (women). On the basis of the evidence available, we do not have a definite proof that T2DM is prevented in any of these trials. However, we can safely conclude that the current evidence strongly favors the notion that lifestyle changes are the primary means to tackle the epidemic of T2DM.

Acarbose↗

[Blood levels of true insulin and immunoreactive insulin in evaluating beta-cell function with arginine stimulation test].

OBJECTIVE: To investigate the difference between serum true insulin (TI) and immunoreactive insulin (IRI) in evaluating islet beta-cell function and insulin resistance. METHODS: The arginine stimulation test was performed in 141 individuals, including 35 with normal glucose tolerance (NGT) and 106 with type 2 diabetes (T2DM). Plasma glucose (PG), TI, IRI and proinsulin (PI) levels were measured; the incremental value of TI/PG, (TI+PI)/PG and IRI/PG (delta TI/PG, delta(TI+PI)/PG and deltaIRI/PG) and the area under curve of TI/PG, (TI+PI)/PG and IRI/PG (AUC [TI/PG], AUC[(TI+PI)/PG] and AUC [IRI/PG]) after arginine stimulation were calculated to evaluate beta-cell function. RESULT: There were positive correlations of delta TI/PG with delta (TI+PI)/PG and delta IRI/PG in both NGT and T2DM patients (r=0.68 - 0.99, P<0.01). The similar correlations of AUC [TI/PG] with AUC [(TI+PI)/PG] and AUC [IRI/PG] were also shown (r=0.62 - 0.99, P<0.01). delta TI/PG was correlated with AUC [TI/PG] in two groups (NGT r=0.96, T2DM r=0.82, P<0.01). HOMA-IRTI, HOMA-IR(TI+PI) and HOMA-IRIRI in T2DM were higher than those in NGT (P<0.01). After arginine stimulation T2DM subjects mainly presented insulin resistance and decreased insulin secretion. CONCLUSION: The determination of TI may be more accurate than IRI in evaluating beta-cell function and insulin resistance.

Adult↗

Common Molecular Mechanisms and Candidate Drug Targets in Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease.

This study examined the mechanisms underlying the comorbidity between type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), while identifying potential therapeutic targets. Common differentially expressed genes (C-DEGs) between T2DM and ASCVD were extracted from the GSE78721 and GSE12288 datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, protein-protein interaction (PPI) network construction, hub gene identification, and Drug-Gene Interaction Database (DGIdb) analysis were conducted. The association between hub C-DEGs and immune-infiltrating cells was analyzed using the CIBERSORT method. Expression levels of hub C-DEGs were quantified through qRT-PCR and Western blot analyses. A total of 32 C-DEGs were identified, comprising 20 upregulated and 12 downregulated genes. C-DEGs were predominantly enriched in key pathways, including viral myocarditis, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. PPI analysis revealed 29 nodes and 39 edges, leading to the identification of eight hub C-DEGs (HSP90B1, PLAU, SLPI, TOP3A, NCF4, PRF1, TUBA1C, and CS) across both datasets. Furthermore, hub C-DEGs (TOP3A, SLPI, NCF4, PRF1, and PLAU) demonstrated significant correlations with immune-infiltrating cell levels. Drugs specifically targeting these hub C-DEGs present promising candidates for the treatment of T2DM and ASCVD. Additionally, the expression of hub C-DEGs at both mRNA and protein levels was validated in patients with T2DM and ASCVD. An integrated bioinformatics analysis facilitated the screening of candidate therapeutic targets, mechanisms, and drugs for T2DM and ASCVD, offering new insights into molecular therapies for these conditions.

Diabetes Mellitus, Type 2↗

Genetic and Lifestyle Factors Influence High 1-Hour Plasma Glucose, a Predictor of Type 2 Diabetes Mellitus.

BACKGRUOUND: High 1-hour plasma glucose (1-h PG) level has been proposed by the International Diabetes Federation to identify high-risk individuals and diagnose type 2 diabetes mellitus (T2DM). In a longitudinal cohort, we examined T2DM risk, &#x3b2;-cell function, and the effects of genetic and lifestyle factors on high 1-h PG. METHODS: We analyzed 7,464 participants without T2D at baseline from a community-based prospective cohort in Korea, who underwent biennial 2-h 75-g oral glucose tolerance tests over 14 years. Incident T2D risk were assessed across 1-h PG groups: < 155, 155-208, and &#x2265; 209 mg/dL. In 6,588 participants with at least two 1-h PG measurements, we analyzed 1-h PG trajectories by T2D polygenic risk score (PRS; low, 1st quintile; intermediate, 2nd-4th quintiles; high, 5th quintile) and lifestyle, assessed using Life's Essential 8. RESULTS: Compared to the <155 mg/dL group, hazard ratios for T2DM were 3.34 (95% confidence interval [CI], 2.99 to 3.74; P<0.001) for 155-208 mg/dL, and 6.81 (95% CI, 5.81 to 7.98; P<0.001) for &#x2265;209 mg/dL. Both groups had lower baseline disposition index compared to the <155 mg/dL group (57.3% and 72.7%, respectively; both P<0.001). Higher T2DM PRS was associated with elevated baseline 1-h PG (low: 131 mg/dL, intermediate: 141 mg/dL, high: 151 mg/dL) and faster increase in 1-h PG (1.36 vs. 1.85 vs. 2.21 mg/dL/year; all P<0.001). Importantly, healthy lifestyle attenuated the rate of increase across all PRS groups. CONCLUSION: High 1-h PG predicts T2DM risk and is associated with &#x3b2;-cell dysfunction. The 1-h PG level is influenced by genetic risk and can be modified with a healthy lifestyle.

Humans↗

Type 2 diabetes mellitus, hyperlipidemia, and extremity lesions in California mice (Peromyscus californicus) fed commercial mouse diets.

BACKGROUND AND PURPOSE: We characterized abnormalities of carbohydrate and lipid metabolism and determined whether those metabolic abnormalities are associated with extremity lesions in California mice (Peromyscus californicus). METHODS: Blood samples were evaluated for glucose, cholesterol, triglyceride, and insulin concentrations. Necropsy and histologic evaluation were done on selected mice, including staining pancreatic sections for insulin. Physical examinations also were performed. RESULTS: California mice were found to have Type 2 diabetes mellitus (T2DM). Sections of pancreas from diabetic and prediabetic mice had pathologic changes consistent with T2DM. After six months of feeding a low-fat diet, mice were normoglycemic, normotriglyceridemic, and normocholesterolemic. Some mice remained hyperinsulinemic. Traumatic lesions were not associated with T2DM. CONCLUSIONS: California mice develop diet-related T2DM when fed a diet containing 25.8% kcal from fat. California mice may be a useful animal model of human T2DM, and traumatic lesions result from housing California mice in multiple male groups.

Animal Feed↗

HDL oxidability and its protective effect against LDL oxidation in Type 2 diabetic patients.

Low density lipoprotein (LDL) oxidation is a crucial step in the atherosclerotic process. High density lipoprotein (HDL)-associated enzymes such as paraoxonase could exert a protective effect on LDL oxidation in the arterial wall, an effect which could be impaired in Type 2 diabetes mellitus (T2DM). We studied copper-induced oxidation in LDL and HDL isolated from 17 T2DM patients with fair glycaemic control and HDL-cholesterol within normal range and 17 healthy normolipidaemic control subjects. To evaluate the effect of HDL on LDL oxidation in diabetic and control subjects, we assessed copper-induced oxidation in HDL/LDL mixtures, with each lipoprotein isolated from the same subject. Relationships with HDL chemical composition, alpha-tocopherol content and serum paraoxonase activity were investigated. Oxidation was promoted by lipoprotein incubation with copper and then thiobarbituric acid reactive substances (TBARS), conjugated diene production and electrophoretic mobility in agarose gel were measured. In T2DM subjects HDL oxidation was higher than in controls. However, HDL from diabetics was as effective as control HDL to inhibit LDL oxidation. Neither HDL chemical composition nor serum paraoxonase activity showed any difference as compared to control subjects. In contrast, HDL from T2DM subjects showed a higher alpha-tocopherol content which positively correlated with HDL oxidability. Paraoxonase activity positively and strongly correlated with HDL inhibitory effect on LDL oxidation in patients and controls belonging to the heterozygous activity phenotype. Besides, LDL oxidability showed no differences between patients and controls. These results suggest that fairly-controlled T2DM patients with HDL-cholesterol levels within normal range show: 1) normal HDL ability to inhibit LDL oxidation related to normal paraoxonase activity; 2) higher HDL oxidability in spite of its high alpha-tocopherol content, which could favour tocopherol-mediated peroxidation and 3) normal LDL oxidability possibly due to the lack of significant lipoprotein structural alterations.

Adult↗

Carotid intima-media thickness in patients with Type 2 diabetes and hypercholesterolemia.

Both patients with Type 2 diabetes mellitus (T2DM) and with hypercholesterolemia have a more extensive and accelerated atherosclerosis with higher common carotid artery intima-media thickness (CIMT) values than the general population. The aim of this study was to compare the CIMT in polygenic hypercholesterolemia (HP; n=41: 30 females and 11 males, aged 52+/-15 yr) and in T2DM (n=43: 22 females and 21 males, aged 59+/-11 yr), with a duration of disease less than 5 yr and no evidence of coronary heart disease. A control group (C) of 40 sex- and age-matched healthy subjects was studied. We evaluated the CIMT on the far wall of the distal segment of the common carotid arteries on sites free of plaque. The mean of the CIMT measurements (Tmean; 9 on each side) and the maximal CIMT measured (Tmax) were used as the representative values for each subject. Tmax values were 0.96+/-0.2 mm and 0.82+/-0.2 mm in T2DM and HP, respectively, which were significantly higher than C (0.74+/-0.1 mm). Corresponding values of Tmean were 0.8+/-0.1 mm and 0.71+/-0.2 mm, both significantly higher than C (0.68+/-0.1 mm). In HP, both Tmax and Tmean values were positively correlated to age (p=0.0001 and p=0.0001, respectively), body mass index (BMI; p=0.05 and p=0.05, respectively), presence of hypertension (p=0.003 and p=0.0008, respectively) and fibrinogen (p=0.0009 and p=0.001, respectively); Tmean was also correlated to apolipoprotein B (ApoB; p=0.03). The multiple "stepwise" regression analysis revealed fibrinogen and age as the only significant determinants of Tmax and Tmean. In T2DM Tmax and Tmean were positively correlated to age only (p=0.04 and p=0.01, respectively). In conclusion, T2DM patients have a more accelerated atherosclerosis than subjects with HP. This is evident after a short duration of disease, probably for a longer latency period of disease and the presence of multiple risk factors.

Age Factors↗

[The UCSNP44 variation of calpain 10 gene on NIDDM1 locus and its impact on plasma glucose levels in type 2 diabetic patients].

OBJECTIVE: To study the contribution of single nucleotide polymorphism-UCSNP44 at calpain-10 gene (CAPN-10) on NIDDM1 locus to type 2 diabetes mellitus (T2DM) in Chinese. METHODS: 276 Chinese living in Shanghai, 148 with normal glucose tolerance (NGT) and 128 with T2DM were given 75 g glucose. O, 30, 60, 120, and 180 minutes later their plasma glucose (PG), insulin (INS), C-peptide (CP), and free fatty acids (FFA) were measured and the areas under curve (AUC) were calculated. The islet beta-cell insulin secretion and tissue insulin sensitivity were estimated by formulae of homeostasis model assessment and increment ratio of insulin to glucose levels 30 minutes after glucose challenge. The CAPN-10 UCSNP44 as well as UCSNP43 were genotyped by automated DNA direct sequencing. RESULTS: (1) The major genotype of CAPN-10 UCSNP44 in persons with NGT was TT (with a frequency of 0.82); the major allele was T (0.91). The most frequent genotype combination between UCSNP44 and UCSNP43 was TT-GG (corresponding to haplotype combination TG/TG) (0.64). The most frequent haplotype was TG (0.80). The D value for linkage disequilibrium between UCSNP44 and UCSNP43 was -0.11. (2) The frequencies of UCSNP44 and UCSNP44/UCSNP43 haplotype combination did not differ significantly between subjects with NGT and those with T2DM. (3) The PG levels in T2DM subjects with UCSNP44 TT genotype both at fasting and after glucose challenge were statistically significantly higher than those in subjects with non-TT (TC + CC) genotype, especially the PG levels 0, 60, 120, and 180 minutes after glucose challenge (P = 0.036, 0.040, 0.020, and 0.017) and the PG-AUC (P = 0.013). The PG levels and PG-AUC 0 and 120 minutes after glucose challenge were still significant after adjusted with age, sex, and body mass index and waist circumference. Similar results were observed in comparison between the TG/TG and TG/CG subgroups of UCSNP44/UCSNP43 haplotype combination. In addition, T2DM subjects with UCSNP44 TT genotype had lower CP levels after glucose challenge than those with non-TT genotype. However, the difference became not statistically significant after adjusted with above-mentioned variables. CONCLUSION: The variation of CAPN-10 UCSNP44 has an impact on plasma glucose levels at fasting and after glucose challenge in subjects with type 2 diabetes. The relevant mechanism remains to be elucidated.

Blood Glucose↗

Correlation between angiotensin II type 1 receptor gene polymorphism and type 2 diabetes mellitus complicated by hypertension.

OBJECTIVE: To elucidate the correlation between angiotensin II type 1 receptor (AT1R) gene polymorphism and type 2 diabetes mellitus (T2DM) complicated by hypertension. METHODS: AT1R gene polymorphism was determined by PCR in 132 T2DM patients complicated by hypertension and 107 normotensive T2DM patients. RESULTS: The frequencies of AA and AC genotypes in the 2 groups were 88.79% vs 96.97% and 11.21% vs 3.03% respectively, and those for A and C allele were 94.39% vs 98.48% and 5.61% vs 1.51%, showing significant difference between the 2 groups (P<0.05). It was suggested that AT1R gene polymorphism was associated with T2DM complicated by hypertension, and the patients had significantly prolonged courses of DM when complicated by hypertension. Normotensive DM patients did not differ from DM patients with only elevated diastolic blood pressure in terms of AT1R-A1166-C gene polymorphism, but showed significant difference from DM patients with elevated systolic blood pressure. CONCLUSION: AT1R gene contributed to T2DM complicated by hypertension, but is only associated with cases of elevated systolic blood pressure.

Adult↗

The impact of prandial glucose regulation in practice.

Post-prandial hyperglycaemia, which occurs early in the development of impaired glucose tolerance and Type 2 diabetes mellitus (T2DM), has been receiving increased attention recently. Post-prandial hyperglycaemia is likely to promote or aggravate fasting hyperglycaemia and contributes entirely to HbA1c elevation, which is associated with microvascular and macrovascular complications in people with T2DM. Moreover, post-prandial hyperglycaemia is coupled with coagulation activation and may be associated with an increased risk of cardiovascular disease in people with or without diabetes. For these reasons, reduction of post-prandial hyperglycaemia is an important target in patients with impaired glucose tolerance or T2DM. Several treatments have therefore been developed to reduce post-prandial hyperglycaemia; of these, repaglinide, a prandial glucose regulator taken orally before each meal, is now available. Drugs that reduce post-prandial hyperglycaemia significantly also decrease HbA1c (up to 2% with repaglinide) and fasting glucose concentrations (up to 3.9 mmol/l with repaglinide), with consequent decreases in coagulation activation and, in some studies, post-prandial lipidaemia. In clinical trials in patients with T2DM, repaglinide significantly reduced 2-hr post-prandial glucose concentrations and significantly reduced the risk of hypoglycaemia, compared with sulphonylureas, especially when participants missed or postponed a meal. Treatment with the prandial glucose regulator repaglinide allows patients with T2DM to have a more flexible lifestyle, which is likely to improve their quality of life and compliance.

Blood Glucose↗

[The association of paraoxonase 2 gene C311S variant with ischemic stroke in Chinese type 2 diabetes mellitus patients].

OBJECTIVE: To investigate the association between the C311S polymorphism of paraoxonase 2 (PON2) gene and ischemic stroke in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: A case-control study of 279 Chinese subjects (including 162 T2DM with or without ischemic stroke and 117 non-diabetic control) was performed. Genotype frequencies of C311S polymorphism were studied by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) analysis with DdeI digestion. RESULTS: C311S polymorphism of PON2 gene was detected in Chinese with the C/S allele frequencies 0.145 and 0.855. The frequency distribution showed significant difference between Chinese and Asian Indian. Furthermore, the genotype distribution (SS, CS and CC) of the PON2 C311S gene polymorphism exhibited a significant difference between T2DM patients complicated with ischemic stroke and T2DM without ischemic stroke, the former had a significantly higher C allele frequency(P<0.05). CONCLUSION: The above data indicate that the polymorphism at codon 311(Cys --> Ser)in the PON2 gene is associated with ischemic morbidity in Chinese T2DM patients and C allele might be a risk factor.

Adult↗

Fuel metabolism in adult individuals with a wide range of body mass index: effect of a family history of type 2 diabetes.

OBJECTIVE: To evaluate whether a family history of Type 2 diabetes mellitus (T2DM) is associated with changes of fuel metabolism in normal glucose tolerant men and women with a wide range of BMI. DESIGN: Cross-sectional study of resting energy expenditure (REE) and substrate oxidation in adult individuals. SUBJECTS: Ninety-seven normal weight, overweight, and obese men and women, aged 18-45 years: 44 (38 pre-menopausal women and 6 men) with a first-degree family history of T2DM (FH+) and 53 (45 pre-menopausal women and 8 men) with no family history of T2DM (FH-). MEASUREMENTS: REE, fat-free mass (FFM)-adjusted REE (REE/Kg FFM), respiratory quotient (RQ), substrate oxidation (carbohydrates, lipids, and proteins), energy intake, anthropometric parameters, body composition (evaluated by BIA), blood pressure, insulin sensitivity (as calculated by Homeostatic Model Assessment) and metabolic variables (fasting levels of insulin, glucose, and lipids). RESULTS: REE, REE/Kg FFM, and lipid oxidation were lower, whereas carbohydrate oxidation and RQ were higher in FH+ than in FH- individuals. CONCLUSIONS: This study suggests that a family history of T2DM decreases REE, REE/Kg FFM and lipid oxidation, thus possibly contributing to the development of obesity and to the adverse metabolic profile of subjects with a genetic background for T2DM.

Adolescent↗

Studies on antidiabetic effects of cortex Moutan polysaccharide-2b in type 2 diabetes mellitus rats.

AIM: To study the antidiabetic effects of cortex Moutan polysaccharide-2b (CMP-2b) in type 2 diabetes mellitus (T2DM) rats. METHODS: The T2DM model rats were induced by a single intravenous injection of low dose streptozotocin (STZ) and intake of high sucrose-fat diet. CMP-2b was given to T2DM rats daily through gavage for 4-5 weeks. The body weight, water and food intake, fasting blood glucose (FBG), glucose tolerance, plasma lipids, serum insulin, and insulin receptor (Ins R) were determined. RESULTS: Oral administration of CMP-2b significantly decreased water and food intake, FBG, total cholesterol (Tch), and triglyceride (TG), improved the impaired glucose tolerance (IGT), and remarkably raised the number of low affinity InsR and insulin sensitivity index (ISI) in T2DM rats. CONCLUSION: CMP-2b may be useful for treating T2DM and its complications.

Animals↗

Pulmonary functions in patients with type 2 diabetes mellitus & correlation with anthropometry & microvascular complications.

BACKGROUND & OBJECTIVES: The purpose of this study was to evaluate pulmonary functions including respiratory muscle strength in patients with type 2 diabetes mellitus (T2DM) and to determine their correlations with anthropometric profile, glycaemic control, and microangiopathic diabetic complications. METHODS: Twenty nine patients with T2DM and 11 healthy control subjects were divided into the following three groups; (i) T2DM patients with any or a combination of microangiopathy(ies) (retinopathy, nephropathy, and peripheral neuropathy) (group 1, n=12); (ii) T2DM patients without any complications (group 2, n = 17); and (iii) a healthy control group (group 3, n=11). All patients were assessed with anthropometry, glycosylated haemoglobin (HbA1C), and lipid profile. Pulmonary functions were measured by spirometry. Pulmonary diffusion capacity for carbon monoxide (DLco) was measured by the steady state method. The presence of diabetic nephropathy was determined by 24 h protein excretion. RESULTS: A significant reduction of DLco was observed in group 1 (P<0.001), as compared to the other groups. There were no differences among the three groups for other pulmonary functions; forced vital capacity, forced expired volume in one second, peak expiratory flow rate, and maximal static inspiratory and expiratory pressures. Significant correlations were observed between DLco and the following parameters in group 1; HbA1c (r=0.62, P<0.05), total cholesterol level (r = -0.44, P<0.05) and creatinine clearance (r=0.42, P<0.05). INTERPRETATION & CONCLUSION: The present study shows that the impairment of pulmonary diffusion capacity for carbon monoxide was common in T2DM Asian Indian patients having microangiopathy. Pathophysiologically, it could be related to glycaemic control or dyslipidaemia. Correlation of % BF with DLCo needs to be explored further.

Adult↗