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Of the various types of diabetes mellitus, non-insulin-dependent diabetes (NIDDM) is by far the most common and is increasing rapidly in many populations around the world. It is a heterogeneous disorder, characterized by a genetic predisposition and interaction between insulin resistance and decreased pancreatic beta-cell function. There is a strong association between the presence of obesity and low levels of physical exercise and the development of NIDDM. However, NIDDM may also develop in lean individuals and the incidence increases significantly with increasing age. A diagnosis of impaired glucose tolerance or gestational diabetes is a strong predictor for future development of NIDDM and should signal appropriate interventions to prevent or delay the progression to NIDDM. NIDDM is frequently associated with other conditions such as hypertension, hypertriglyceridemia and decreased high-density lipoprotein which are additional risk factors for atherosclerosis and cardiovascular disease. The 'insulin resistance syndrome', which includes obesity, NIDDM, hypertension, hyperinsulinemia and dyslipidemia is a major and increasing cause of morbidity and mortality in many populations. In addition, people with NIDDM and poor glycemic control may develop severe microvascular complications of diabetes, including retinopathy, nephropathy and neuropathy. Appropriate diet, weight control and increased physical activity will increase insulin sensitivity in insulin resistant patients and are effective treatments for patients with NIDDM or may prevent the development of NIDDM in susceptible individuals. If these measures are unsuccessful, then oral hypoglycemic agents or insulin therapy may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NIDDM--the devastating disease. 852 17

Dyslipidaemia is a common finding in the syndrome of gestational diabetes mellitus (GDM). Free fatty acids (FFA) can cause insulin resistance and have a toxic effect on beta cell function. GDM is a syndrome due to insulin resistance and the purpose of this study was to examine FFA levels in pregnancy. For this purpose samples were taken from 44 consecutive women with GDM and 36 consecutive controls. The women with GDM had similar levels of insulin, triglycerides and total cholesterol to the controls but a significant elevation in FFA; 0.70 (0.33) mmol/L versus 0.29 (0.12) mmol/L (p < 0.0001).
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PMID:Free fatty acids and gestational diabetes mellitus. 888 45

Five thousand five hundred seventy-two newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (3,225 men and 2,347 women; mean age, 58.5 years) were recruited through the General Practitioners (GPs) network in France. All had persistent hyperglycemia after a preliminary 3-month period with dietary and life-style modification. Gliclazide (80 to 320 mg/d) was then prescribed as diabetic pharmacotherapy for 2 years. Additional therapy for hypertension and dyslipidemia was started if necessary. The aim of the study was mainly to determine the feasibility of a GP-directed protocol for the monitoring and treatment of newly diagnosed NIDDM patients, and to assess the effectiveness of diabetic therapy in this cohort. Diabetes was diagnosed in 78% of the cohort during routine screening. Among the women, 6.5% had a history of gestational diabetes. Eighteen percent of the patients had a parental history of diabetes, and the dominant maternal role in the genesis of NIDDM was confirmed. High blood pressure (Joint National Committee V criteria) was found at inclusion in 38.8% of the whole cohort. Hyperlipidemia was known in 44.6%. A history of stroke was present in 1.6% of the patients, and coronary heart disease (CHD) in 6.3%. These data support the relationship between the atherogenic state and development of NIDDM. Microalbuminuria defined as urinary albumin excretion (UAE) of at least 20 mg/L was found in 29.6% of the patients, and retinopathy in 9.8%. Among the included patients, 23% did not complete the study and were excluded from the efficacy analysis. Of these, 14% (808 patients) had only baseline evaluation data and 9% (499 patients) withdrew later. Comparison of mean baseline and final results in study completers uncovered a significant improvement in fasting blood glucose ([FBG] 182 +/- 48 v 137 +/- 40 mg/dL), post prandial blood glucose ([PPBG] 209 +/- 68 v 162 +/- 52 mg/dL), and hemoglobin A1c ([HbA1c] 8.7% +/- 2.5% v 7.3% +/- 2.0%). A slight improvement in total cholesterol (228 +/- 44 v 222 +/- 41 mg/dL), body mass index ([BMI] 28.5 +/- 4.7 v 27.9 +/- 4.5 kg/m2), and waist to hip ratio (0.99 +/- 0.1 v 0.98 +/- 0.1) was observed. There was a decrease in the percentage of patients with high blood pressure (38.5% v 30.7%). A mild increase in the prevalence of retinopathy (10.2% v 11.8%) was noted during the study, while the incidence of microalbuminuria remained unchanged (30.2% v 29.5%). In conclusion, the data indicate that the GPs involved in this study were able to successfully monitor and manage NIDDM patients in accordance with a standardized protocol. Gliclazide appeared to be an effective and well-tolerated treatment. The high prevalence of chronic diabetic complications at diagnosis emphasizes the delay encountered in reaching the diagnosis of NIDDM and the problems associated with this delay. In addition to the classic risk factors for NIDDM exhibited in this patient cohort, we have identified CHD and a maternal genetic component as further potential predicting factors.
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PMID:Management of newly diagnosed non-insulin-dependent diabetes mellitus in the primary care setting: effects of 2 years of gliclazide treatment--the Diadem Study. 943 56

Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice.
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PMID:The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks. 1035 18

The purpose of this study was to examine characteristics associated with the insulin metabolic syndrome, including insulin resistance, abnormal glucose tolerance, dyslipidemia, obesity, and elevated blood pressure, among women who have experienced gestational diabetes. 39 nondiabetic, young (20-42 years), postpartum (3-18 months) white women were recruited from obstetrical clinics. Twenty-one women had a history of gestational diabetes; 18 had uncomplicated pregnancies. Multivariate analyses revealed a significant difference between groups in insulin resistance (M, measured by euglycemic clamp) and insulin levels (from an oral glucose tolerance test), with insulin resistance showing a statistically stronger difference than insulin levels. Groups also differed significantly when compared on a set of variables associated with insulin metabolic syndrome: glucose tolerance, triglycerides, blood pressure, and body-mass index. Using insulin resistance as a covariate eliminated these group differences, suggesting that insulin resistance is the key factor underlying insulin metabolic syndrome. The higher risk of later developing type 2 diabetes and hypertension in women who have a history of gestational diabetes is explicable by their poorer profile on variables associated with insulin metabolic syndrome, and appears to be attributable to insulin resistance. Thus, insulin resistance appears to distinguish young women at risk for cardiovascular disease.
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PMID:History of gestational diabetes, insulin resistance and coronary risk. 1061 62

To assess the usefulness of random capillary plasma glucose (RCPG) measurement in screening for diabetes mellitus in high-risk subjects, a RCPG measurement and a 75-g oral glucose tolerance test (OGTT) were performed in 684 women and 164 men, aged 16-76 years (mean+/-SD: 41.9+/-11.3 years). Risk factors included family history of diabetes in first degree relatives (53.8%), obesity (BMI > or =27 kg/m(2)) in 37.9%, dyslipidemia (78.4%), hypertension, i.e. BP > or =140/90 mmHg (28.5%), and history of gestational diabetes mellitus (16.6%). According to the 1997 ADA/1998 WHO Consultation criteria for a full OGTT, 118 cases (13.9%) were found to have diabetes. Each of 19 cases with RCPG > or =13.3 mmol/l had diabetes according to OGTT, 4.7% of 427 cases with RCPG<6.1 mmol/l had diabetes. Among 402 subjects with RCPG between 6.1 and <13.3 mmol/l, 19.7% were found to have diabetes. Thus, 446 (52.6%) of 848 subjects would have been saved from OGTT if RCPG was used as a screening test, in comparison to 33.1% if the cutpoints for RCPG (12.2 and 5.5 mmol/l) recommended by WHO Study Group (1985)/WHO Consultation (1998) were applied. Therefore, RCPG measurement is a useful screening test for the screening of diabetes mellitus in high-risk subjects.
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PMID:Random capillary plasma glucose measurement in the screening of diabetes mellitus in high-risk subjects in Thailand. 1116 92

Insulin resistance can be linked to diabetes, hypertension, dyslipidemia, cardiovascular disease and other abnormalities. These abnormalities constitute the insulin resistance syndrome. Because resistance usually develops long before these diseases appear, identifying and treating insulin-resistant patients has potentially great preventive value. Insulin resistance should be suspected in patients with a history of diabetes in first-degree relatives; patients with a personal history of gestational diabetes, polycystic ovary syndrome or impaired glucose tolerance; and obese patients, particularly those with abdominal obesity. Present treatment consists of sensible lifestyle changes, including weight loss to attain healthy body weight, 30 minutes of accumulated moderate-intensity physical activity per day and increased dietary fiber intake. Pharmacotherapy is not currently recommended for patients with isolated insulin resistance.
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PMID:Insulin resistance syndrome. 1127 52

Genetic, environmental, and metabolic risk factors are interrelated and contribute to the development of type 2 diabetes mellitus. A strong family history of diabetes mellitus, age, obesity, and physical inactivity identify those individuals at highest risk. Minority populations are also at higher risk, not only because of family history and genetics, but also because of adaptation to American environmental influences of poor dietary and exercise habits. Women with a history of gestational diabetes as well as their children are at greater risk for progressing to type 2 diabetes mellitus. Insulin resistance increases a person's risk for developing impaired glucose tolerance and type 2 diabetes. Individuals who have insulin resistance share many of the same risk factors as those with type 2 diabetes. These include hyperinsulinemia, atherogenic dyslipidemia, glucose intolerance, hypertension, prothrombic state, hyperuricemia, and polycystic ovary syndrome. Current interventions for the prevention and retardation of type 2 diabetes mellitus are those targeted towards modifying environmental risk factors such as reducing obesity and promoting physical activity. Awareness of risk factors for developing type 2 diabetes will promote screening, early detection, and treatment in high-risk populations with the goal of decreasing both microvascular and macrovascular complications.
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PMID:Risk factors for type 2 diabetes mellitus. 1180 65

Obesity, insulin resistance, and endothelial dysfunction closely coexist throughout the natural history of type 2 diabetes. They all can be identified not only in people with type 2 diabetes, but also in various groups at risk for the disease, such as individuals with impaired glucose tolerance, family history of type 2 diabetes, hypertension, dyslipidemia, prior gestational diabetes, or polycystic ovary syndrome. Whereas their evident association cannot fully establish a cause-effect relationship, fascinating mechanisms that bring them closer together than ever before are rapidly emerging. Central or abdominal obesity leads to insulin resistance and endothelial dysfunction through fat-derived metabolic products, hormones, and cytokines. Insulin resistance leads to endothelial dysfunction through the frequent association with traditional cardiovascular risk factors and through some more direct novel mechanisms. Some specific and shared insulin signaling abnormalities in muscle, fat, and endothelial cells, as well as some new genetic and nontraditional factors, may contribute to this interesting association. Some recent clinical studies demonstrate that nonpharmacological and pharmacological strategies targeting obesity and/or insulin resistance ameliorate endothelial function and low-grade inflammation. All these findings have added a new dimension to the association of obesity, insulin resistance, and endothelial dysfunction that may become a key target in the prevention of type 2 diabetes and cardiovascular disease.
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PMID:Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. 1462 47

Impaired glucose tolerance and impaired fasting glucose form an intermediate stage in the natural history of diabetes mellitus. From 10 to 15 percent of adults in the United States have one of these conditions. Impaired glucose tolerance is defined as two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in fasting patients. These glucose levels are above normal but below the level that is diagnostic for diabetes. Patients with impaired glucose tolerance or impaired fasting glucose have a significant risk of developing diabetes and thus are an important target group for primary prevention. Risk factors for diabetes include family history of diabetes, body mass index greater than 25 kg per m2, sedentary lifestyle, hypertension, dyslipidemia, history of gestational diabetes or large-for-gestational-age infant, and polycystic ovary syndrome. Blacks, Latin Americans, Native Americans, and Asian-Pacific Islanders also are at increased risk for diabetes. Patients at higher risk should be screened with a fasting plasma glucose level. When the diagnosis of impaired glucose tolerance or impaired fasting glucose is made, physicians should counsel patients to lose 5 to 7 percent of their body weight and engage in moderate physical activity for at least 150 minutes per week. Drug therapy with metformin or acarbose has been shown to delay or prevent the onset of diabetes. However, medications are not as effective as lifestyle changes, and it is not known if treatment with these drugs is cost effective in the management of impaired glucose tolerance.
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PMID:Impaired glucose tolerance and impaired fasting glucose. 1571 15


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