AIMS: to examine the incidence rate of progression to Type 2 diabetes and baseline prognostic risk factors, focusing on hypertension and antihypertensive medication, in a cohort (n=207) with impaired glucose tolerance (IGT). METHODS: after 2 and 4.6 (1. 9-6.4) years new cases of diabetes were diagnosed by the oral glucose tolerance test (OGTT). Hypertension (BP 160/95 or antihypertensive medication) was included in multiple regression analyses to assess the effect of risk factors on the development of diabetes. RESULTS: diabetes developed in 32 subjects (19%), an incidence of 41/1000 (95% CI 28-57/1000) person-years. In univariate analyses, progression to diabetes was associated with a high (>9.0 mmol/l) 2-h OGTT value (P=0.008), a high fasting insulin (>12.0 mU/l) level (P=0.000), a high triglyceride (>/=1.3 mmol/l) level (P=0.028), a high BMI (>/=28.0 kg/m(2)) (P=0.013) and hypertension (P=0.003). The risk for the development of diabetes was not increased in hypertensive subjects without antihypertensive medication compared with normotensive subjects (OR 0.8, 95% CI 0.3-2. 6). However, it was increased in subjects with on medication, especially diuretics alone or in combination with other drugs. Hypertensive subjects on diuretics had higher levels of fasting insulin and triglycerides and higher BMIs at baseline than normotensive subjects. After adjustment for 2-h OGTT, fasting insulin, triglycerides and BMI, the OR for diabetes was 7.7 (95% CI 2.1-28.2) in hypertensive subjects using diuretics alone or in combination with other drugs and 2.6 (95% CI 1.0-6.7) in those using other drugs compared with normotensive subjects. The OR of diabetes corresponding to a one-unit increase in the 2-h OGTT concentration was 2.5 (95% CI 1.6-4.0) in the whole cohort. CONCLUSIONS: the rate of progression from IGT to Type 2 diabetes in this population was similar to that seen in other studies among Caucasian populations. The use of antihypertensive medication, especially diuretics, and a high 2-h OGTT level were significant predictors of subsequent deterioration to diabetes.
Impaired insulin secretion has a strong genetic component. In this study we investigated whether the 12Glu9 polymorphism in the gene encoding the alpha2B-adrenergic receptor ( ADRA2B) is associated with insulin secretion and/or the incidence of Type 2 diabetes in individuals with impaired glucose tolerance.
We investigated a total of 506 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Participants were randomly assigned to an intervention group or a control group. Anthropometric measurements and an oral glucose tolerance test were performed at baseline and at annual follow-up. In a subgroup of patients (n=83), a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at baseline.
All patients had similar anthropometric measurements and insulin and glucose levels at baseline. Multiple logistic regression analysis revealed significant interaction (p=0.003) between study group and genotype across the entire study population. In the control group, subjects with the Glu9 allele had an increased risk of developing Type 2 diabetes compared with subjects with the Glu12/12 genotype (odds ratio [OR]=2.68, 95% CI 1.02-7.09, p=0.047 for Glu12/12, and OR=5.17, 95% CI 1.76-15.21, p=0.003 for Glu9/9). This increased risk was not observed in the intervention group, who showed significant weight loss during the trial. In the subgroup who underwent the FSIGT, subjects with the Glu9/9 genotype showed the lowest acute insulin response (p=0.005 for trend).
The 12Glu9 polymorphism of ADRA2B is associated with impaired first-phase insulin secretion and may predict the development of Type 2 diabetes in subjects with impaired glucose tolerance who are not subjected to a lifestyle intervention.
AIM: Overall and central obesity are associated with disorders in lipid and glucose metabolism, insulin resistance, hypertension, atherosclerosis and type 2 diabetes. Waist circumference and abdominal sagittal diameter have been suggested as the best simple anthropometric indexes of abdominal visceral fat accumulation. The aim of the present study was to test the association of neck circumference with abdominal and general obesity as well as with insulin resistance related factors. METHOD: Neck circumference was measured in addition to the traditional anthropometric measures and blood lipids, insulin and glucose concentrations and blood pressure. RESULTS: The prevalence rates of disorders in lipid or glucose metabolism and high fasting insulin concentrations were highest in the highest quintiles of all the anthropometric measures. CONCLUSION: We conclude that neck circumference is associated with the metabolic disorders related to insulin resistance. The measurement of neck circumference could be useful in clinical screening for persons at an enhanced risk for insulin resistance.
Prevalence and incidence of known diabetes mellitus in Finnish subjects aged 30 years or over in 1970-1987 were investigated using a nationwide register of drug recipients and four population surveys. On the basis of the drug-register data, the prevalence of drug-treated diabetes in men increased from 1.5% in 1970 to 2.8% in 1987. In women, the prevalence increased from 2.1% in 1970 to 3.0% in 1979 and declined thereafter slightly to 2.7% in 1987. The increase in the prevalence of drug-treated diabetes was mainly due to the increase of diabetes in the age groups 60 years and older. The prevalence of all known diabetic subjects in the population studies increased from 2.1% in the health examination survey of 1966-1972 (n = 38,676) to 3.5% in the interview survey of 1976 (n = 10,657) and to 4.5% in the health examination survey of 1979-1980 (n = 7,217) but decreased to 3.3% in the interview survey in 1987 (n = 9,522). The increased prevalence of obesity in men and better survival may be important factors contributing to the increasing prevalence rates of diabetes in Finnish subjects aged 30 years and over.
Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The Finnish Diabetes Prevention Study.
Type 2 diabetes is a complex disorder with strong heritability. The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor [IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 [PC-1]; K121Q, insulin receptor substrate [IRS-1]; G972R, insulin receptor substrate 2 [IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 alpha [PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study.
We screened for the polymorphisms in 490 overweight subjects with impaired glucose tolerance whose DNA was available from the Finnish Diabetes Prevention Study. These subjects were randomly allocated into a control group and an intervention group characterised by intensive, individualised diet and exercise.
In carriers of the GAA1013GAA genotype of IGF-1R, the R972 allele of IRS-1 and the D1057D genotype of IRS-2, lifestyle intervention did not lead to significant differences in weight loss between the intervention and control groups, implying a role of these risk genotypes in the regulation of body weight. We observed a statistically significant difference in the conversion rate from IGT to diabetes between the genotypes of the IGF-1R gene (GAG1013GAG: 18.6%, GAG1013GAA: 10.4%, GAA1013GAA: 19.5%, p=0.033). Common polymorphisms in the insulin, PC-1 and PI3K genes did not regulate weight change or conversion to diabetes.
The common polymorphisms of the IGF-1R, IRS-1 and IRS-2 genes may modify the weight change response to a lifestyle intervention but not the conversion from IGT to Type 2 diabetes, whereas IGF-1R may also regulate the risk of developing Type 2 diabetes.
Laparoscopic Roux-en-Y gastric bypass (RYGB) induces a more favorable metabolic profile than expected by weight loss alone. In this study, we investigated the effect of RYGB on serum bile acid levels and their relation to clinical outcomes.
We included 30 obese patients who underwent RYGB (BMI?=?46.1?±?5.9 kg/m(2)). Clinical measurements and laboratory determinations were performed before surgery and 1 year after surgery. Fasting serum bile acids were measured by an enzymatic method and individual bile acids were quantified by HLPC-tandem mass spectrometry. Indirect calorimetry was performed to measure the rates of energy expenditure and substrate oxidation.
Fasting total serum bile acid levels increased twofold after RYGB (pre, 3.68?±?2.03 vs. post, 7.06?±?9.65 µmol/l, +92 %, p?=?0.002). This increase in total bile acids was accompanied by a decrease in conjugated bile acids, which correlated with decreased glucose oxidation (r?=?0.571, p?=?0.002) and with increased lipid oxidation (r?=?-0.626, p?=?0.0004). The change in taurine-conjugated bile acids correlated with altered DIO2 mRNA expression in adipose tissue (r?=?-0.498, p?=?0.013) potentially linking bile acid conjugation to substrate oxidation through DIO2.
Fasting serum bile acid levels increase after RYGB. More specifically, changes in bile acid conjugation after RYGB associate with altered energy metabolism.
Finland has marked regional differences in the occurrence of coronary heart disease (CHD). Although the causes for these differences in CHD mortality and morbidity in the Finnish population are unknown, it offers an excellent opportunity to investigate the effects of non-insulin-dependent diabetes mellitus (NIDDM) on CHD risk in two populations differing significantly with respect to the occurrence of CHD. Therefore, we carried out a 7-year prospective population-based study including a large number of patients with NIDDM (East Finland: 253 men and 257 women; West Finland: 328 men, 221 women) and corresponding non-diabetic subjects (East Finland: 313 men, 336 women; West Finland: 325 men, 399 women). In both study populations the presence of NIDDM increased significantly the risk for CHD events (CHD mortality or all CHD events including CHD mortality or non-fatal myocardial infarction). Diabetic men had 3-4 fold higher and diabetic women 8-11-fold higher risk for CHD than corresponding non-diabetic subjects. Both non-diabetic and diabetic subjects had odds ratios (East vs West) for CHD events of about 2 indicating a similar East-West difference in the CHD risk. Regional difference was quite similar in men and women. These results imply that factors related to NIDDM, independently of conventional risk factors and the occurrence of atherothrombosis in the background population, must play a major role in the pathogenesis of atherosclerotic vascular disease in NIDDM diabetes.
The aim of this study was to compare the effect of family history of non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD) as risk factors for CHD morbidity and mortality. Altogether, 394 siblings of NIDDM probands and non-diabetic probands, with and without CHD, were followed for 8 years with respect to CHD events in a prospective population-based study. The baseline study was conducted from 1983 to 1985. Age- and sex-adjusted cumulative occurrence of CHD events was higher in the siblings of the probands with CHD and with NIDDM (13.1%; P = 0.037) and in the siblings of the probands with CHD and without NIDDM (15.4%; P = 0.054), compared with the siblings of the probands without NIDDM and without CHD (4.8%). The incidence of fatal CHD events tended to be higher in a group with a family history of NIDDM and CHD, but the trend was not statistically significant. In univariate logistic regression analyses, a family history of CHD was positively associated with cumulative occurrence of CHD events (odds ratio 2.53, P = 0.009), whereas a family history of NIDDM had no significant association (odds ratio 1.39, P = 0.312). After adjustment for age, sex, family history of NIDDM and major cardiovascular risk factors, the association between family history of CHD and cumulative occurrence of CHD events remained significant (odds ratio 2.25, P = 0.048). In conclusion, the present study indicates that a family history of CHD is a stronger predictor of future CHD events than a family history of NIDDM.
The association between fasting plasma insulin level and coronary heart disease (CHD) was studied in 909 non-insulin-dependent diabetic (NIDDM) patients, aged 45-64 years, and in 1,373 nondiabetic control subjects. Both diabetic and nondiabetic subjects with various manifestations of CHD had higher plasma insulin levels than did subjects free of CHD. By plasma insulin quintiles formed according to values in nondiabetic subjects, the age-adjusted prevalence of CHD defined by symptoms and/or electrocardiographic changes in diabetic men was 48.2% in quintiles I + II (lowest), 54.8% in quintiles III + IV, and 65.7% in quintile V (highest) (p = 0.006). The respective prevalences in diabetic women were 53.5%, 59.1%, and 73.3% (p = 0.004); in nondiabetic men, 28.1%, 33.7%, and 43.3%, respectively (p = 0.016); and in nondiabetic women, 28.1%, 34.9%, and 44.3%, respectively (p = 0.007). An essentially similar association was observed between plasma insulin level and definite or possible myocardial infarction (MI). In diabetic subjects, a positive association between plasma insulin level and CHD manifestations was also found when insulin strata were formed using quintile cutoff points determined separately from diabetic subjects. The association between plasma insulin level and the prevalence of CHD or MI disappeared or was weaker, especially in men, when adjustment was made for body mass index, hypertension, and triglyceride or high density lipoprotein (HDL) cholesterol level. The association between high plasma insulin level and CHD was significant in diabetic subjects with a body mass index greater than 27 kg/m2 but not in those diabetics with a body mass index less than or equal to 27 kg/m2. A significant clustering of hypertension, high triglyceride values, and low HDL cholesterol levels was observed in diabetic subjects in the highest insulin quintiles. The results suggest that hyperinsulinemia is an indicator of CHD in both NIDDM patients and nondiabetic subjects. Hyperinsulinemia may be directly atherogenic, but it is more probable that hyperinsulinemia reflects insulin resistance, which may be a factor enhancing atherogenesis by causing adverse changes in many CHD risk factors.
The aim of this prospective study was to determine risk factor clusters predicting type 2 diabetes in subjects with and without family history of diabetes by applying factor analyses.
The study population consisted of 309 siblings of diabetic (DM+) or nondiabetic (DM-) probands. Risk factors, including lipids, lipoproteins, blood pressure, and glucose tolerance status, were measured at the baseline study and 8 years later.
Siblings in the DM+ group had a significantly higher risk of diabetes (odds ratio [OR] = 3.25; P = 0.002) than siblings in the DM- group. Altogether, factor analyses revealed four significant factors in both the DM+ and DM- groups (the percentage of cumulative variance explained 62-66%). Of these, factor 1 (percentage of variance, 27-29%) was characterized by high loadings for BMI, hypertension, glucose area, insulin area (the highest loading), and triglycerides in both the DM+ and DM- groups; therefore, factor 1 can be interpreted as a hyperinsulinemia factor. Also, other factors were essentially similar in both groups. Hyperinsulinemia factor was similarly associated with the risk of developing diabetes in the DM+ group (OR = 4.33, 95% CI 2.29-8.19; P