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PubMed2006

Low-carbohydrate and high-fat intake among adult patients with poorly controlled type 2 diabetes mellitus.

OBJECTIVE: This study examined baseline dietary intake, body weight, and physiologic status in patients enrolled in a dietary intervention for type 2 diabetes mellitus (T2DM). METHODS: Dietary, physiologic, and demographic information were collected at baseline from 40 adult patients with poorly controlled T2DM (glycosylated hemoglobin >7%) who participated in a clinical trial at an academic medical center in Worcester, Massachusetts, USA. RESULTS: The average age at enrollment was 53.5 y (SD 8.4), average body mass index was 35.48 kg/m(2) (SD 7.0), and glycosylated hemoglobin was 8.3% (SD 1.2). Participants were predominantly white, married, and employed full time. Forty-eight percent were men. Seventy-eight percent had hyperlipidemia, and 68% had hypertension. Reported baseline daily average energy intake was 1778 kcal (SD 814), daily carbohydrate was 159 g (SD 71.5), and dietary fiber was 11.4 g (SD 5.2). The dietary composition was 35% carbohydrate, 45% fat (15% saturated fat), and 20% protein. The American Diabetes Association (ADA) guidelines recommends 45-65% of energy from carbohydrate, 20-35% from fat (<7% saturated), and 20% from protein. CONCLUSION: These patients reported a low-carbohydrate, low-fiber, high-fat (especially saturated) diet, although they stated they are not following any of the popular low-carbohydrate diets. Patients with T2DM may find the current trend toward reducing weight through low-carbohydrate diets attractive for control of blood glucose, despite ADA recommendations. This dietary pattern may represent a popular trend that extends beyond our particular study and, if so, has serious cardiovascular implications in this vulnerable population of T2DM patients.

Body Mass Index↗
PubMed2006

Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women.

PURPOSE: To study the relation between type 2 diabetes mellitus (T2DM) and incident primary open-angle glaucoma (POAG) in women. DESIGN: Prospective cohort analysis. PARTICIPANTS: Seventy-six thousand three hundred eighteen women enrolled in the Nurses' Health Study (NHS). METHODS: Women enrolled in the NHS from 1980 to 2000 were observed. Eligible participants were at least 40 years old, did not have POAG at baseline, and reported receiving eye examinations during follow-up. Potential confounders were assessed on biennial questionnaires, and a diagnosis of T2DM was confirmed on a validated supplemental questionnaire. During follow-up, 429 self-reported POAG cases confirmed by medical chart review were identified. MAIN OUTCOME MEASURES: Multivariable rate ratios (RRs) of POAG and associated 95% confidence intervals (CIs) obtained from proportional hazards models. RESULTS: After controlling for age, race, hypertension, body mass index, physical activity, alcohol intake, smoking, and family history of glaucoma, T2DM was positively associated with POAG (RR = 1.82 [95% CI = 1.23-2.70]). Nonetheless, the association did not strengthen with longer duration of diabetes: RR = 2.24 (95% CI = 1.31-3.84) for duration < 5 years versus RR = 1.54 (95% CI = 0.90-2.62) for duration > or = 5 years). In secondary analyses, to evaluate the potential for detection bias we controlled for additional factors such as the number of eye examinations, but T2DM remained positively associated with POAG. CONCLUSION: Type 2 diabetes mellitus is associated with an increased risk of POAG in women.

Adult↗
PubMed2004

Comparative genomic analysis of the HNF-4alpha transcription factor gene.

Hepatocyte nuclear factor-4alpha (HNF-4alpha), the gene for the maturity-onset diabetes of the young type 1 (MODY1) form of type 2 diabetes mellitus (T2DM), is within the T2DM-linked region on chromosome 20q12-q13.1 and consequently, is a positional candidate gene for T2DM. Mutations in the coding region of HNF-4alpha are rare in diabetes affected subjects. Altered regulation of HNF-4alpha gene expression, controlled by distant enhancer sequences, may contribute to the development of type 2 diabetes. Comparative sequence analysis was performed between 13 kb of genomic DNA 5' to the P1 promoter sequences of the human, mouse, and rat HNF-4alpha coding sequences. Three regions, located at -10.5 kb (295 bp in length), -6.25 kb (421 bp in length), and -5.36 kb (263 bp in length), have significant sequence identity between the species. These three regions were functionally characterized using the chloramphenicol acetyltransferase (CAT) reporter assay, in which the conserved 5' regions of mouse HNF-4alpha were cloned in front of the herpes simplex virus thymidine kinase promoter driving transcription of the CAT gene. A fragment containing the 421 bp conserved region significantly increased CAT activity in differentiated rat hepatoma cells (13.7-+/-1.9-fold control), while only a modest increase in CAT activity was observed in pancreatic cells (2.5-+/-0.9-fold control; 1.6-+/-0.1-fold control) and dedifferentiated hepatoma cells (1.7-+/-0.4-fold control). The remaining two conserved regions increased CAT activity minimally in pancreatic (1.1-+/-0.1-fold control to 1.9-+/-0.1-fold control) and hepatic (1.6-+/-0.5-fold control to 2.3-+/-0.4-fold control) cell lines. Denaturing high-performance liquid chromatography (DHPLC) was used to search for sequence variants in DNA from 259 T2DM individuals. Two single nucleotide polymorphisms (SNPs) were identified, both of which increased CAT activity in the insulinoma cell lines in the CAT reporter assay (1.4-fold increase over wild-type; 1.7-fold increase over wild-type). These results suggest that comparative sequence analysis can efficiently identify regulatory elements and that sequence variants in regulatory elements of HNF-4alpha can contribute to altered HNF-4alpha gene expression.

Amino Acid Sequence↗
PubMed2006

Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits.

Serum retinol binding protein 4 (RBP4) was recently described as a new adipokine that reduced peripheral and hepatic insulin sensitivity and increased hepatic gluconeogenesis. The RBP4 gene maps to 10q23-24, near a region linked to T2DM in Caucasian and Mexican American populations. Hence, sequence variants that alter RBP4 expression or function could increase T2DM susceptibility and reduce insulin sensitivity. We screened the 6 exons, flanking intronic sequence, and 5' and 3' flanking sequences in 48 Caucasian and 48 African American subjects. We identified 21 SNPs, of which 8 were unique to the African American population. Additional public database SNPs were chosen for regions not screened. We selected SNPs for typing based on frequency, linkage disequilibrium, and location in a putative functional or conserved region. We typed 10 SNPs in 191 Caucasians with T2DM and a family history of T2DM, and 188 euglycemic controls with no family history of diabetes. We similarly typed 14 variants in 182 controls and 353 diabetic individuals of African American ancestry. No single variant was associated with type 2 diabetes in either population (p>0.15 in African Americans, p>0.09 in Caucasians), but a haplotype of 8 common SNPs in Caucasians was significantly increased in type 2 diabetics compared with controls (0.137 vs. 0.076, p=0.008). Furthermore, SNPs -804 and +9476 were associated with reduced insulin secretion, (p=0.01 and 0.001, respectively), and SNP +390 with reduced insulin sensitivity (p=0.0005) in Caucasians. Our data suggest that noncoding SNPs may increase diabetes susceptibility in Caucasians and may contribute to insulin resistance and reduced insulin secretion.

Adult↗
PubMed2002

Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects.

Enhanced platelet function, particularly in response to collagen, is a common occurrence in diabetes that increases the risk of cardiovascular disease. Ginkgo biloba extract is ingested primarily to improve mental focus but it possesses a blood-thinning potential, which has not been well characterized. This study was designed to compare the effect of ingesting G. biloba extract on platelet aggregation in platelet-rich plasma (PRP) and prostanoid urinary excretion in healthy volunteers and subjects with Type 2 diabetes mellitus (T2DM). Before and after ingesting 120 mg of standardized G. biloba extract for 3 months, platelet aggregation was studied in PRP and urinary metabolites of thromboxane B(2) (TXB(2)) and prostacyclin (PGI(2)) were measured. In healthy volunteers (age, 42+/-11 years; BMI, 28.4+/-4.8 kg/m(2); n=28), the ingestion of G. biloba extract significantly increased fasting insulin and C-peptide (10+/-4 vs. 12+/-6 microU/ml, p<0.007 and 1.3+/-0.8 vs. 2.1+/-1.1 ng/ml, p<0.001, respectively) and significantly reduced collagen but not PAF-mediated platelet aggregation, converting 21 of 28 subjects with [COL+/EPI+] platelets to the [COL-/EPI+] phenotype. This was accompanied by a reduction of 11-dehydro-TXB(2) from 12.4+/-6.1 to 10.3+/-6.1 ng/mg Cr (p<0.04) and PGI(2) metabolites (2,3-dinor-6-keto-PGF(1alpha) and 6-keto-PGF(1alpha)) from 2.2+/-0.8 to 1.8+/-0.8 ng/mg Cr (p<0.05). In the T2DM subjects (age, 54+/-8; BMI, 36.6+/-7.9 kg/m(2); n=19), G. biloba ingestion did not affect pancreatic beta-cell function but significantly reduced platelet aggregation, converting 16 of 19 [COL+/EPI+] platelets to the [COL-/EPI+] phenotype. Unlike the healthy volunteers, this was not accompanied by a reduced urinary prostanoid excretion. G. biloba-induced reduction of both classes of prostanoid metabolites in healthy volunteers, but not in T2DM subjects, may suggest a nonselective inhibition of COX-1-mediated TXA(2) in platelets and COX-2-mediated PGI(2) production by the endothelial cells and perhaps platelet-enriched levels of arachidonic acid or COX-1 activity, or both, in T2DM subjects.

6-Ketoprostaglandin F1 alpha↗
PubMed2002

Is there a need for changes in renal biopsy criteria in proteinuria in type 2 diabetes?

Criteria for renal biopsy in proteinuric type 2 diabetes mellitus (T2DM) patients have been not defined. Usually criteria for renal biopsy in type 1 diabetes mellitus (T1DM) are used (microhaematuria, absence of diabetic retinopathy (DR), uncharacteristic change in renal function or immunological abnormalities). The aim of this study was to reconsider the indications for renal biopsy in T2DM using T1DM criteria, to determine whether they are useful in identifying patients with potentially treatable lesions. We studied 127 proteinuric patients with T2DM. Renal biopsy was performed in 35 who met the criteria for biopsy. Biopsy revealed diabetic glomerulopathy (DG) in 29 (83%) (in three associated with nondiabetic renal disease), immunoglobulin A (IgA) glomerulonephritis in three, focal glomerulosclerosis in one and normal glomeruli in two. DG was diagnosed in 17 (74%) of the patients without DR, in 18 (78%) of the patients with microhaematuria and in 10 (67%) of the patients with microhaematuria and without DR. All patients with DR had DG alone, except three with sudden unexpected changes in renal function. We conclude that DG is the most commonly found renal lesion in T2DM patients with proteinuria biopsied according to T1DM criteria, even in patients with microhaematuria or without retinopathy. Thus, these biopsy criteria are not useful in identifying patients with potentially treatable other renal diseases.

Aged↗
PubMed2003

Higher prevalence of type 2 diabetes, metabolic syndrome and cardiovascular diseases in gypsies than in non-gypsies in Slovakia.

OBJECTIVE: Gypsies (or Roma) recently experienced a transition from a traditional to a Westernized lifestyle. Although mortality in this population is 4-fold higher compared with non-Gypsies, very limited information is available on their morbidity especially with regard to non-communicable diseases. Our aim was to determine the prevalence of type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular diseases in Gypsies and non-Gypsies living in the same region of southern Slovakia. MATERIALS AND METHODS: We examined 156 Gypsies and 501 non-Gypsies who participated in a population survey. Age- and sex-standardized prevalence rates were computed for each of the following: T2DM, obesity, hyperlipidemia, hypertension, hyperinsulinemia, elevated albumin/creatinine ratio (ACR), metabolic syndrome and cardiovascular disease. RESULTS: Age-sex standardized prevalence of T2DM was 30% (95% CI=22-39) in Gypsies and 10% (8-13, P=0.0001 for comparison of ethnic groups) in non-Gypsies. Corresponding prevalence of the other variables are: 65% (56-74) and 30% (26-34, P=0.0001) for obesity, 69% (61-76) and 59% (54-63, P=0.04) for hypercholesterolemia, 66% (59-74) and 39% (35-43, P=0.009) for hypertriglyceridemia, 49% (42-56) and 43% (39-47, P=0.1) for hypertension, 33% (26-50) and 8% (2-14, P=0.002) for hyperinsulinemia, 16% (9-22) and 5% (3-7, P=0.0001) for elevated ACR, 20% (12-27) and 4% (3-6, P=0.0001) for metabolic syndrome and 35% (28-43) and 26% (22-29, P=0.004) for cardiovascular disease. CONCLUSIONS: Compared with non-Gypsies, Gypsies had a much higher prevalence of T2DM, metabolic syndrome and cardiovascular disease, which may contribute to their higher mortality.

Adolescent↗
PubMed2001

Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control.

OBJECTIVES: This study was designed to determine whether blood thrombogenicity is related to chronic glycemic control in type 2 diabetes mellitus (T2DM). BACKGROUND: Type 2 diabetes mellitus is associated with accelerated atherosclerosis and a high rate of arterial thrombotic complications. Whether increased blood thrombogenicity is associated with glycemic control has not been properly tested. METHODS: Forty patients with T2DM with hemoglobin A1c (HbA1c) > or =7.5% were selected. Maintaining their current hypoglycemic therapies, patients were randomized into a conservative (diet modification plus placebo) or intensive (diet modification plus troglitazone) hypoglycemic regimen for three months. Blood thrombogenicity was measured at baseline and after three months with the Badimon ex vivo perfusion chamber and assessed as platelet-thrombus formation. The repeated measurements allowed every patient to be his/her own control. RESULTS: Patients in both groups (48% and 74% of the conservative and intensive groups, respectively) improved glucose control (HbA1c reduction > or =0.5%), showing a significant decrease in blood thrombogenicity. A significant positive correlation was observed between the reduction in thrombus formation and the reduction in HbA1c (r = 0.47, p < 0.01). The reduction in HbA1c achieved by both treatments was comparable. Patients without glycemic improvement showed no change in blood thrombogenicity. Improved glycemic control was the only significant predictor of a decrease in blood thrombogenicity. CONCLUSIONS: In T2DM, there is an association between improved glycemic control and blood thrombogenicity reduction. The effect of glycemic control on the thrombotic complications of T2DM patients deserves further investigation.

Analysis of Variance↗
PubMed2003

Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus.

OBJECTIVES: The aim of our study was to assess whether acute, short-term hyperglycemia affects platelet reactivity in patients with Type II diabetes mellitus (T2DM). BACKGROUND: Hyperglycemic spikes are thought to precipitate ischemic events in T2DM. Previous studies have shown in vivo platelet activation in diabetes; however, no studies have assessed whether acute in vivo hyperglycemia induces further activation of platelets. METHODS: In a cross-over, randomized, double-blind study, 12 patients with T2DM underwent 4 h of either acute hyperglycemia (13.9 mmol/l, 250 mg/dl) or euglycemia (5.5 mmol/l, 100 mg/dl). Shear stress-induced platelet activation, P-selectin and lysosomal integral membrane protein (LIMP) expression on platelets in the bleeding-time blood, urinary 11-dehydro-thromboxane B(2) (TxB(2)) excretion, von Willebrand factor:antigen (vWF:Ag), and von Willebrand factor:activity (vWF:activity) were measured before and after hyperglycemia or euglycemia. RESULTS: Shear stress-induced platelet activation, P-selectin and LIMP expression on platelets in the bleeding-time blood, and urinary 11-dehydro-TxB(2) excretion increased significantly after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping. Plasma vWF:Ag and vWF:activity increased strikingly in parallel fashion after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping. CONCLUSIONS: Our data demonstrate that acute, short-term hyperglycemia induces an increased activation of platelets exposed to high shear stress conditions in vitro (filtration method) or in vivo (bleeding time). In vivo platelet activation is reflected by an increased urinary excretion of 11-dehydro-TxB(2). The increased levels of vWF in the circulation correlate with the increase in platelet activation markers and may indicate some degree of causation. Acute, short-term hyperglycemia in T2DM may precipitate vascular occlusions by facilitating platelet activation.

Acute Disease↗
PubMed2004

Cereal grains, legumes and diabetes.

This review examines the evidence for the role of whole grain foods and legumes in the aetiology and management of diabetes. MedLine and SilverPlatter ('Nutrition' and 'Food Science FSTA') databases were searched to identify epidemiological and experimental studies relating to the effects of whole grain foods and legumes on indicators of carbohydrate metabolism. Epidemiological studies strongly support the suggestion that high intakes of whole grain foods protect against the development of type II diabetes mellitus (T2DM). People who consume approximately 3 servings per day of whole grain foods are less likely to develop T2DM than low consumers (<3 servings per week) with a risk reduction in the order of 20-30%. The role of legumes in the prevention of diabetes is less clear, possibly because of the relatively low intake of leguminous foods in the populations studied. However, legumes share several qualities with whole grains of potential benefit to glycaemic control including slow release carbohydrate and a high fibre content. A substantial increase in dietary intake of legumes as replacement food for more rapidly digested carbohydrate might therefore be expected to improve glycaemic control and thus reduce incident diabetes. This is consistent with the results of dietary intervention studies that have found improvements in glycaemic control after increasing the dietary intake of whole grain foods, legumes, vegetables and fruit. The benefit has been attributed to an increase in soluble fibre intake. However, prospective studies have found that soluble fibre intake is not associated with a lower incidence of T2DM. On the contrary, it is cereal fibre that is largely insoluble that is associated with a reduced risk of developing T2DM. Despite this, the addition of wheat bran to the diets of diabetic people has not improved indicators of glycaemic control. These apparently contradictory findings might be explained by metabolic studies that have indicated improvement in glucose handling is associated with the intact structure of food. For both grains and legumes, fine grinding disrupts cell structures and renders starch more readily accessible for digestion. The extent to which the intact structure of grains and legumes or the composition of foods in terms of dietary fibre and other constituents contribute to the beneficial effect remains to be quantified. Other mechanisms to help explain improvements in glycaemic control when consuming whole grains and legumes relate to cooking, type of starch, satiety and nutrient retention. Thus, there is strong evidence to suggest that eating a variety of whole grain foods and legumes is beneficial in the prevention and management of diabetes. This is compatible with advice from around the world that recommends consumption of a wide range of carbohydrate foods from cereals, vegetables, legumes and fruits both for the general population and for people with diabetes.

Blood Glucose↗
PubMed2005

Cost-effectiveness of orlistat for the treatment of overweight and obese patients in Ireland.

OBJECTIVE: To assess the cost-effectiveness of orlistat plus a calorie-controlled diet compared with a calorie-controlled diet alone for the treatment of overweight and obese patients in Ireland. DESIGN: Economic modelling techniques using published international efficacy data and Irish cost data were used to estimate the cost-effectiveness of orlistat in obese patients when only responders to treatment (ie achieve 5% weight loss after 3 months of treatment) continue orlistat after 3 months. The model incorporated known relationships between weight loss and quality of life (utility) gain, and weight loss and reduction in risk of type 2 diabetes (T2DM) to predict the impact of weight loss on quality-adjusted-life-years (QALYs) gained and on the onset of T2DM. The costs associated with each treatment arm included the acquisition cost of orlistat, cost of a calorie-controlled dietary programme and monitoring and treatment costs associated with T2DM. An Irish health-care perspective was taken for the analysis, based on 2003 costs. SUBJECTS: Weight loss data on 1386 patients from five pivotal orlistat clinical trials with at least 12 months duration were pooled (two American and three primarily European studies). All the studies were randomized, placebo-controlled, multicentre trials with a similar design. The inclusion criteria were BMI > or =28 kg / m(2), age > or =18 y, no diagnosed T2DM and the ability to lose 2.5 kg in weight during the introductory period. MEASUREMENTS: Cost effectiveness was modelled from these data and presented as incremental cost per QALY. RESULTS: When orlistat treatment plus a calorie-controlled diet was compared with a calorie-controlled diet alone, the incremental cost per year was euro 478. The number needed to treat (NNT) to gain one QALY was estimated to be 35. The incremental cost per QALY gained was within the range considered cost-effective at euro 16,954. Sensitivity analysis demonstrated an incremental cost per QALY of euro 11,000-35,000 under a variety of assumptions. CONCLUSIONS: Our model suggests that orlistat is effective and cost-effective in obese patients, if after 3 months of treatment, only treatment responders continue treatment.

Adult↗
PubMed2002

Genetics of type 2 diabetes and insulin resistance: knowledge from human studies.

Both type 2 diabetes mellitus (T2DM) and insulin resistance are complex traits in which multiple gene effects and metabolic and environmental factors combine to contribute to the overall pathogenesis of these conditions. This complexity has complicated the search for susceptibility genes and has led to different but complementary approaches being used for the detection of gene effects. These include the study of monogenic cases of insulin resistance and T2DM, association studies of candidate genes and genome-wide scans. The peroxisome proliferator-activated receptor gamma (PPARgamma) and calpain-10 (CAPN10) genes have recently been identified as T2DM susceptibility genes, and the lessons learnt from these studies are helping to shape future strategies to search for additional susceptibility genes in T2DM and insulin resistance.

Calpain↗
PubMed2003

Metabolic and cardiovascular effects of very-low-calorie diet therapy in obese patients with Type 2 diabetes in secondary failure: outcomes after 1 year.

AIMS: To evaluate the short-term and 1-year outcomes of an intensive very-low-calorie diet (VLCD) on metabolic and cardiovascular variables in obese patients with Type 2 diabetes (T2DM) and symptomatic hyperglycaemia despite combination oral anti-diabetic therapy +/- insulin, and to assess patient acceptability and the feasibility of administering VLCD treatment to this subgroup of patients in a routine practice setting. METHODS: Forty obese patients with T2DM (22 M, mean age 52 years, body mass index (BMI) 40 kg/m2, duration of T2DM 6.1 years) and symptomatic hyperglycaemia despite combination oral therapy (n = 26) or insulin + metformin (n = 14) received 8 weeks of VLCD therapy (750 kcal/day) followed by standard diet and exercise advice at 2-3-month intervals up to 1 year. Insulin was discontinued at the start of the VLCD, and anti-diabetic therapy was adjusted individually throughout the study, including (re)commencement of insulin as required. RESULTS: Immediate improvements in symptoms and early weight loss reinforced good compliance and patient satisfaction. After 8 weeks of VLCD, body weight and BMI had fallen significantly: 119 +/- 19-107 +/- 18 kg and 40.6-36.6 kg/m2, respectively, with favourable reductions in serum total cholesterol (5.9-4.9 mm), blood pressure (10/6 mmHg) and fructosamine (386 +/- 73-346 +/- 49 microm) (equates to an HbA1c reduction of approximately 1%). Sustained improvements were evident after 1 year, with minimal weight regain, e.g. mean body weight 109 +/- 18 kg and BMI 37 +/- 4 kg/m2. Glycaemic control tended to deteriorate after 1 year. CONCLUSIONS: The absence of a control group is a major limitation, but the results indicate that 8 weeks of VLCD treatment may be effective and well tolerated in symptomatic obese patients with T2DM in secondary failure, producing sustained cardiovascular and metabolic improvements after 1 year. VLCD therapy is a treatment option that deserves greater consideration in this difficult-to-treat patient population.

Adult↗
PubMed2003

Lipid and protein oxidation contribute to a prothrombotic state in patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) is associated with enhanced lipid oxidation and persistent platelet activation. We investigated whether oxidant stress (OS) also affects circulating proteins and is associated with an abnormal coagulative pattern. In 72 type 2 DM (T2DM) patients, urinary 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane B2 (TXM) were measured as markers of lipid peroxidation and platelet activation, respectively. The carbonyl content of plasma proteins (PCARB) was measured as global index of protein oxidation. 8-Iso-PGF2alpha and PCARB levels were higher in DM patients than in controls (P < 0.05). Likewise, both TXM and prothrombin F1+2 levels were higher in diabetics (P < 0.05). By contrast, anticoagulant markers, such as activated protein C, protein C activation peptide, and soluble thrombomodulin (TM) were depressed in T2DM (P < 0.05). In conclusion, OS in T2DM involves circulating proteins and is associated with an unbalanced promotion of procoagulant reactions. These effects in concert with platelet activation may contribute to atherothrombotic complications in T2DM.

Aged↗
PubMed2002

Glucagon dose-response curve for hepatic glucose production and glucose disposal in type 2 diabetic patients and normal individuals.

This study sought to examine whether enhanced hepatic sensitivity to glucagon contributes to impaired glucose homeostasis in subjects with type 2 diabetes mellitus (T2DM). Eight T2DM and 9 age-, weight-, and gender-matched nondiabetic subjects received a 4-hour glucagon infusion at the rates of 0.2, 0.5, 2, 6, and 8 ng. kg(-1). min(-1) while maintaining the plasma insulin concentration constant at the basal level with exogenous infusions of somatostatin and insulin. On the evening prior to study, diabetic subjects received a low-dose insulin infusion at a rate designed to maintain euglycemia and this infusion rate was continued until the end of the glucagon infusion study on the following day. Each glucagon infusion study was performed on a separate day and in random order. 3-(3)H-glucose was infused in all studies to measure endogenous glucose production (EGP) and the rate of whole body glucose disposal. During the first 2 hours (0 to 120 minutes) of glucagon infusion, EGP increased sharply in both groups, and the initial rate of rise in EGP was higher in control versus diabetic subjects. During the last 2 hours (120 to 240 minutes) of glucagon infusion, EGP in the diabetics tended to be higher than controls during the 3 lower glucagon infusion rates and this difference reached statistical significance (P <.05 to.01) during the 6 and 8 ng. kg(-1). min(-1) infusions. During the 2 hours following cessation of glucagon (240- to 360-minute time period), the stimulation of glucose disappearance from plasma was impaired (P <.05) during all 5 glucagon infusion rates in the diabetics compared to controls. We conclude that in T2DM patients, the initial (0 to 120 minutes) stimulation of hepatic glucose output (which primarily reflects glycogenolysis) by glucagon is not enhanced in T2DM patients. The late (120 to 240 minutes) stimulation of hepatic glucose output (which primarily reflects gluconeogenesis) by glucagon tends to be increased, especially at supraphysiologic plasma glucagon concentrations.

Diabetes Mellitus, Type 2↗
PubMed2006

Preliminary evidence of FABP2 A54T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German cohort.

The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.

Adult↗
PubMed2005

Low-glycaemic diets and health: implications for obesity.

The present review considers the background to terminology that relates foods, glycaemia and health, including 'available carbohydrate', 'glycaemic index' (GI), 'glycaemic glucose equivalent', 'glycaemic response index' and 'net carbohydrate', and concludes that central to each of these terms is 'glycaemic load' (GL). GL represents the acute increase in exposure of tissue to glucose determined by foods; it is expressed in ingested glucose equivalents (per 100 g fresh weight or per serving), and is regarded as independent of the state of glucose metabolism from normal to type 2 diabetes mellitus (T2DM). Ad libitum studies in overweight or obese adults and children show that low-GL diets are associated with marked weight benefits, loss of adiposity and reduced food intake. Weight benefits appear on low-glycaemic v. high-glycaemic available carbohydrates, unavailable v. available carbohydrates and protein v. available carbohydrate. Energy intake immediately after lowering of meal GL via carbohydrate exchanges is apparent only after a threshold cumulative intake of >2000 MJ. Various epidemiological and interventional studies are discussed. A relationship between GL and the development of T2DM and CHD is evident. Studies that at first seem conflicting are actually consistent when data are overlaid, such that diets with a GL of >120 glucose equivalents/d would appear to be inadvisable. Whereas certain studies might place GI as being slightly stronger than GL in relation to T2DM risk, this situation appears to be associated with observations in a lower range of GL or when the range of GI is too narrow for accuracy; nevertheless, authors emphasise the importance of GL. Among the studies reviewed, GL offers a better or stronger explanation than GI in various observations including body weight, T2DM in nurses, CHD, plasma triacylglycerols, HDL-cholesterol, high-sensitivity C-reactive protein and protein glycation. Where information is available, the associations between risk factors and GL are either similar or stronger in the overweight or obese, as judged by BMI, and apply to both body weight and blood risk factors. The implications tend to favour a long-term benefit of reducing GL, for which further study is necessary to eliminate any possibility of publication bias and to establish results in clinical trials with overweight and obese patients.

Body Weight↗
PubMed2002

Methods for quantifying self-monitoring blood glucose profiles exemplified by an examination of blood glucose patterns in patients with type 1 and type 2 diabetes.

The maintenance of glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively) is commonly assisted by devices for self-monitoring of blood glucose (SMBG) that store multiple BG determinations. However, besides average BG, no other SMBG characteristics are routinely computed. We describe several SMBG-based measures that quantify the extent and rate of patients' BG excursions into hypoglycemia and hyperglycemia and can be used as markers for patients' vulnerability to hypoglycemia and BG irregularity. These markers are applied to analyze data from patients with T1DM (n = 277) and T2DM (n = 323), all of whom used insulin. T1DM and T2DM patients were matched by HbA(1c), gender, and number of SMBG readings/day. On average, 230 SMBG readings and three HbA(1c) assays were collected for each subject over 3 months. Compared with T2DM, patients with T1DM diabetes had (1) more extreme low and high BGs, (2) greater risk for severe hypoglycemia as quantified by the Low BG Index, (3) faster descent into hypoglycemia as quantified by the risk rate of change/hour, and (4) greater BG irregularity as computed by BG rate of change/hour and BG SD (all p levels < 0.0001). SMBG data allow for computing and frequent updating of various idiosyncratic diabetes characteristics and risk factors. The use of such computations may assist in optimizing patients' glycemic control.

Adult↗