Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Given these similarities, we questioned whether there may be a common underlying mechanism predisposing to islet and cerebral amyloid. To address this, we first examined the prevalence of type 2 diabetes in a community-based controlled study, the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease versus control subjects without Alzheimer disease. In addition to this clinical study, we performed a pathological study of autopsy cases from this same community to determine whether there is an increased prevalence of islet amyloid in patients with Alzheimer disease and increased prevalence of cerebral amyloid in patients with type 2 diabetes. Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease control subjects n = 138) were classified according to fasting glucose concentration (FPG) as nondiabetic (FPG <110 mg/dl), impaired fasting glucose (IFG, FPG 110-125 mg/dl), and type 2 diabetes (FPG >126 mg/dl). The mean slope of FPG over 10 years in each case was also compared between Alzheimer disease and non-Alzheimer disease control subjects. Pancreas and brain were examined from autopsy specimens obtained from 105 humans (first, 28 cases of Alzheimer disease disease vs. 21 non-Alzheimer disease control subjects and, second, 35 subjects with type 2 diabetes vs. 21 non-type 2 diabetes control subjects) for the presence of islet and brain amyloid. Both type 2 diabetes (35% vs. 18%; P < 0.05) and IFG (46% vs. 24%; P < 0.01) were more prevalent in Alzheimer disease versus non-Alzheimer disease control subjects, so 81% of cases of Alzheimer disease had either type 2 diabetes or IFG. The slope of increase of FPG with age over 10 years was also greater in Alzheimer disease than non-Alzheimer disease control subjects (P < 0.01). Islet amyloid was more frequent (P < 0.05) and extensive (P < 0.05) in patients with Alzheimer disease than in non-Alzheimer disease control subjects. However, diffuse and neuritic plaques were not more common in type 2 diabetes than in control subjects. In cases of type 2 diabetes when they were present, the duration of type 2 diabetes correlated with the density of diffuse (P < 0.001) and neuritic plaques (P < 0.01). In this community cohort from southeast Minnesota, type 2 diabetes and IFG are more common in patients with Alzheimer disease than in control subjects, as is the pathological hallmark of type 2 diabetes, islet amyloid. However, there was no increase in brain plaque formation in cases of type 2 diabetes, although when it was present, it correlated in extent with duration of diabetes. These data support the hypothesis that patients with Alzheimer disease are more vulnerable to type 2 diabetes and the possibility of linkage between the processes responsible for loss of brain cells and beta-cells in these diseases.
 ...
PMID:Increased risk of type 2 diabetes in Alzheimer disease. 1474

Metabolic syndrome is a cluster of cardiovascular risk factors. Pathogenesis of metabolic syndrome implies 3 potential etiological mechanisms: obesity and adipose tissue disorders, insulin resistance, and a constellation of independent factors. Clinical recognition of the metabolic syndrome is based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, other components commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (plasminogen activator inhibitor [PAI]-I and fibrinogen). Cardiovascular disease (CVD) is the primary clinical outcome of metabolic syndrome. Additionally, risk for type 2 diabetes is higher. Diabetes is itself a major risk factor for CVD. ATP III criteria for diagnosis of metabolic syndrome provide a practical tool to identify patients at increased risk for CVD. World Health Organization (WHO) and American Association of Clinical Endocrinologists (AACE) criteria require further oral glucose testing if IFG and diabetes are absent. IGT on OGTT denotes greater risk for diabetes than does metabolic syndrome without elevated fasting glucose.
 ...
PMID:Metabolic syndrome--new insights into a growing entity. 1552 16

To learn more about the factors that regulate adipokines in diabetes, we examined fasting plasma concentrations of adiponectin and C-reactive protein (CRP) in well-characterized groups of age-matched individuals classified as: (1) type 2 diabetes; (2) impaired fasting glucose or mild diabetes (IFG/mild DM); (3) obese, matched for body mass index (BMI); and (4) non-obese. Diabetic subjects were also studied on no phamacologic treatment, after 3 months randomization to metformin or glyburide, and after 3 months crossover to the opposite drug. CRP decreased and adiponectin increased progressively between subjects in groups 1 through 4. CRP was significantly associated with percent (r = 0.45) and total (r = 0.50) fat, insulin sensitivity as S(I) (r = -0.39) or homeostasis model assessment of insulin resistance [HOMA (IR)] (r = -0.36), and hemoglobin A(1c) (HbA(1c)) (r = 0.41). The relationship of CRP to percent fat appeared to be logarithmic and log CRP varied with percent fat independent of gender. Adiponectin concentration was significantly associated with insulin sensitivity as S(I) (r = 0.55) or HOMA (IR) (r = -0.46). Adiponectin concentrations were higher among women overall (all groups included) but not in women classified as type 2 diabetes. Although mean adiponectin was higher in subjects classified as non-obese compared to obese, adiponectin, in sharp contrast to leptin (previously reported data) and to CRP, varied markedly when expressed as a function of adiposity. Multiple regression models confirmed the strong relationship of adiponectin to insulin sensitivity, as well as the relationships of CRP to adiposity and insulin sensitivity. Glyburide treatment of diabetes decreased CRP and did so even though body weight increased. We conclude that both CRP and adiponectin correlate strongly to S(I). CRP, in contrast to adiponectin, is far more dependent on adiposity. The relationship between CRP (like leptin) and gender depends on how CRP is expressed relative to adiposity. Our data raise the possibility that gender differences in adiponectin may be lost in diabetes. Finally, pharmacologic treatment of diabetes may modulate CRP independent of adiposity.
 ...
PMID:Adiponectin and C-reactive protein in obesity, type 2 diabetes, and monodrug therapy. 1553 1

We sought to identify lifestyle behaviours which influence risk of impaired glucose metabolism, IGM (newly diagnosed type 2 diabetes, impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) or insulin resistance (IR) in a predominantly Maori community, and applied the McAuley formula to determine whether it predicts high risk individuals amongst this community. Three hundred and seventy one participants completed a lifestyle and dietary behaviour questionnaire and oral glucose tolerance test. Clinical variables, microalbuminuria, fasting glucose, insulin and lipids were measured. Diabetes, IFG and IGT were defined according to WHO criteria. IR was defined using the McAuley formula. Those with IGM and those with IR showed similar risk factor attributes. Odds ratios (95% CI) for development of IGM and IR were 0.43 (0.21-0.88) and 0.51 (0.33-0.80), respectively, for regular physical activity, and 0.55 (0.26-1.15) and 0.59 (0.37-0.96), respectively, for two or more dietary behaviours characterized by a high intake of fibre. Regular physical activity and a diet characterized by a high intake of dietary fibre were found to reduce risk of newly diagnosed IGM or IR. The McAuley formula appears to predict high-risk individuals in a predominantly Maori population as it does in European populations.
 ...
PMID:Insulin resistance and impaired glucose metabolism in a predominantly Maori community. 1619 17

Low socioeconomic status (SES) is associated with type 2 diabetes. Inflammatory markers like C-reactive protein (CRP) are predictive of diabetes. It is unclear, whether inflammation may be a mechanism linking low SES to type 2 diabetes. In the population-based KORA Survey 2000, 766 men and 710 women aged 55 to 74 years were randomly selected in the Augsburg region (Southern Germany). An index for SES was defined using education, occupation, and income. In women but not in men, increased CRP concentrations were found with lower SES (p<0.01). This significant trend was no longer observed after adjusting for BMI and waist circumference (p=0.23). Low SES was significantly associated with the age-adjusted odds of having type 2 diabetes both in men (OR; 95%CI: 1.35; 1.14-1.60) and in women (2.01; 1.37-2.96). The risk of having diabetes associated with low SES was only slightly changed after adjusting for CRP, which was itself significantly related to diabetes. In multivariate analyses, adjusting for age, obesity, physical activity, smoking, alcohol intake, and CRP, low SES yielded only a borderline statistical significance in women (p=0.07), whereas no significant association with diabetes remained in men (p=0.14). After CRP was dropped from the full model, there was no change in the OR obtained for low SES (men: 1.30; 0.92-1.83; women: 1.54; 0.97-2.45). Low SES was not related to prediabetes (IFG, IGT), whereas CRP was significantly associated with diabetes precursors. In conclusion, inflammation appears not to play a major role linking low SES and type 2 diabetes in the elderly population.
 ...
PMID:Is inflammation a causal chain between low socioeconomic status and type 2 diabetes? Results from the KORA Survey 2000. 1645 Feb 7

Amrita Diabetes and Endocrine Population Survey (ADEPS) was conducted as a community-based cross-sectional survey to assess the prevalence of undetected diabetes mellitus (DM) and impaired glucose tolerance (IGT) and their possible relationship with various risk factors in an urban South Indian population. An initial house-to-house survey of adults between ages 18 and 80 years (n = 3069) was followed by a second phase consisting of health check-up and biochemical evaluations of participants (n = 986). DM and IGT were diagnosed as per WHO criteria. Reported prevalence of known diabetes mellitus in the survey was 9.0% (276/3069); (M-8.7% and F-9.2%). Among the screened subjects who underwent blood testing, the prevalence of newly diagnosed diabetes was 10.5%. The prevalence of IGT was 4.1% and IFG was 7.1%. Increasing age, obesity, positive family history of diabetes, abnormal subscapular triceps skin fold ratio and presence of acanthosis nigricans (AN) were all found to be associated with increased risk of DM. The finding of high prevalence of newly detected DM and IGT in this population of Kerala with the highest standards of health care and literacy level compared to other states of India, emphasizes the need for routine screening of high-risk groups for early detection of the disease. A simple cutaneous sign, acanthosis nigricans was independently associated with increased risk of type 2 diabetes in this survey and can be used as indication for screening for DM and IGT.
 ...
PMID:Prevalence of known and undetected diabetes and associated risk factors in central Kerala--ADEPS. 1673 Aug 47

Partially inconsistent data exist on mutual relations between nontraditional atherosclerotic risk factors, including the magnitude of insulin resistance (IR), as well as on their relevance for atherogenesis in the metabolic syndrome. Subjects exhibiting combined impaired fasting glucose and impaired glucose tolerance (IFG/IGT) are exposed to an exceptionally high risk for atherogenesis and development of type 2 diabetes mellitus. Because of islet Beta-cell dysfunction, the usefulness of commonly used indices of IR is limited in IFG/IGT. Our aim was to assess the relationship between extent of angiographic coronary artery disease (CAD) and nontraditional atherosclerotic risk factors (including IR by a clamp-based golden standard method) in IFG/IGT. Fifty-three subjects (32 men, 21 women; mean age, 55 +/- 11 years) with stable angina, preserved left ventricular systolic function, and IFG/IGT were divided into 3 groups: group A (no coronary stenoses >50%, n = 22), group B (1-vessel CAD, n = 15), and group C (2/3-vessel CAD, n = 16). Insulin sensitivity was quantified by a hyperinsulinemic euglycemic clamp technique and expressed as M. M value, plasma homocysteine (Hcy) level, and asymmetric dimethyl-L-arginine (ADMA)/L-arginine ratio were independent determinants of CAD extent as shown by forward stepwise discriminant function analysis. Compared with group A (M = 32.7 +/- 9.3 micromol/kg fat-free mass [FFM] per minute; Hcy, 8.1 +/- 1.4 micromol/L), lower M and higher Hcy levels were found in group B (M = 16.9 +/- 8.2 micromol/kg FFM per minute, P < .001; Hcy, 11.2 +/- 2.9 micromol/L, P = .003) and C (M = 16.4 +/- 7.8 micromol/kg FFM per minute, P < .001; Hcy, 12.8 +/- 3.9 micromol/L, P < .001). The ADMA/L-arginine ratio was increased in group C (0.0078 +/- 0.0011) compared with group A (0.0063 +/- 0.0013, P = .03) and B (0.0058 +/- 0.0012, P = .01). Multivariate correlates (P < .05) of plasma Hcy concentrations were M (beta = -.34 +/- .12, P = .008), creatinine clearance (beta = -.23 +/- .10, P = .03) and fasting insulin (beta = .25 +/- .12, P = .04). This indicates an additive contribution of IR, plasma Hcy, and elevated ADMA/L-arginine ratio to the extent of angiographic CAD in combined IFG/IGT.
 ...
PMID:Nontraditional atherosclerotic risk factors and extent of coronary atherosclerosis in patients with combined impaired fasting glucose and impaired glucose tolerance. 1716 Dec 29

Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes, few studies have examined this issue independently of other lifestyle modifications. The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes (IGT and/or IFG). A detailed search of MEDLINE (1966-2006) and EMBASE (1980-2006) found 279 potentially relevant studies, eight of which met the inclusion criteria for this review. All eight studies were controlled trials in individuals with impaired glucose tolerance. Seven studies used a multi-component lifestyle intervention that included exercise, diet and weight loss goals and one used a structured exercise training intervention. Four studies used the incidence of diabetes over the course of the study as an outcome variable and four relied on 2-h plasma glucose as an outcome measure. In the four studies that measured the incidence of diabetes as an outcome, the risk of diabetes was reduced by approximately 50% (range 42-63%); as these studies reported only small changes in physical activity levels, the reduced risk of diabetes is likely to be attributable to factors other than physical activity. In the remaining four studies, only one reported significant improvements in 2-h plasma glucose even though all but one reported small to moderate increases in maximal oxygen uptake. These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal.
 ...
PMID:The role of physical activity in the management of impaired glucose tolerance: a systematic review. 1772 76

Thiazide diuretics may cause multiple metabolic abnormalities. The authors investigated the effects of varying doses of hydrochlorothiazide (HCTZ) on arterial elasticity and metabolic parameters in patients with hypertension (HTN), HTN and impaired fasting glucose (HTN+IFG), and HTN and type 2 diabetes mellitus (HTN+DM). The patients received low and high doses of HCTZ. Systolic and diastolic blood pressures declined significantly during the first 3 months in all patients, but no additional decrease was seen following the increase in HCTZ dose. In HTN, large artery elasticity index and small artery elasticity increased during the study. In HTN+IFG, large artery elasticity index increased without improvement in small artery elasticity index. In HTN+DM, both large artery elasticity index and small artery elasticity index did not improve during follow-up. Low-dose HCTZ improves arterial elasticity in hypertensive patients, but this effect is diminished with concomitant DM or IFG. The HCTZ dose increase worsened parameters of glucose metabolism and did not further decrease blood pressure or improve arterial elasticity.
 ...
PMID:Treatment of hypertension with thiazides: benefit or damage-effect of low- and high-dose thiazide diuretics on arterial elasticity and metabolic parameters in hypertensive patients with and without glucose intolerance. 1768 58

In healthy individuals, the ability of the pancreatic islets to sense and respond appropriately to changes in plasma glucose levels maintains plasma glucose levels within a narrow range despite broad fluctuations in nutrient intake and variable "demand" for insulin imposed by changes in insulin sensitivity. This ability of the pancreatic islets is lost in type 2 diabetes (T2DM). For studies on the pathophysiology of T2DM, methods for analyzing islet function are therefore required. Many methods of varying degrees of complexity have been developed and used to measure pancreatic beta-cell function in humans and to characterize the defects existing in patients with T2DM or precursors thereof (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]). Significant, although perhaps less progress has been made toward development of methods to characterize alpha-cell function. This work presents an overview of clinical measures of islet function, from simple static measures such as HOMA-beta to the more complex dynamic measures such as those utilizing stepped hyperglycemic clamps and acute administration of arginine to obtain more detailed information regarding the interaction of glucose and non-glucose secretagogues. We emphazise the need for accurate measures of alpha-cell function, and we discuss the strengths and limitations of the various methods, highlighting the many aspects of both alpha- and beta-cell function that become impaired during development of T2DM.
 ...
PMID:Clinical measures of islet function: usefulness to characterize defects in diabetes. 1847 60


<< Previous 1 2 3 4 5 6 Next >>