Non-Alcoholic Fatty Liver Disease Markers Associated with Fasting Serum Insulin and Urinary Albumin Excretion Independent of Fasting Plasma Glucose.

OBJECTIVE: We examined the association between non-alcoholic fatty liver disease (NAFLD) markers and fasting serum immunoreactive insulin (FIRI) and urinary albumin excretion (UAE). SUBJECTS AND METHODS: This study comprised Periods I and II from January 2007 to May 2009, and from June 2009 to December 2011, respectively. After excluding people with ethanol intake ≥210 g/week in men and ≥140 g/week in women, 961 people (613 men, 348 women; mean age: 44 years) were included. We evaluated the fatty liver using ultrasonography score (FLUS) and measured liver enzymes. RESULTS: The mean observation period was 25 ± 9 months. We stratified people into two groups by fasting plasma glucose (FPG) in Period I. The cutoff point between the lower FPG and higher FPG was 100 mg/dL. In regression analysis, serum alanine aminotransferase (ALT) (p < 0.001), FLUS (p < 0.001) and γ-glutamyl transpeptidase (GGTP) (p = 0.022) in Period I were independently associated with FIRI in Period II, whereas in all participants FPG was not. ALT (p < 0.001) and GGTP (p = 0.001) were also independently associated with UAE in people with FPG < 100 mg/dL in Period II. CONCLUSIONS: Some NAFLD markers were associated with FIRI and UAE independently of fasting plasma glucose.

Low-frequency and very low-intensity ultrasound decreases blood pressure in hypertensive subjects with type 2 diabetes.

BACKGROUND: Despite lifestyle interventions and various types of anti-hypertension agents, hypertension remains difficult to control in some patients with type 2 diabetes. As a noninvasive device-based approach for the treatment of clinic hypertension, we examined the effects of low-frequency and low-intensity ultrasound (500 or 800kHz, 25mW/cm(2)) applied to the forearm on blood pressure (BP) and pulse rate in Japanese subjects with type 2 diabetes and hypertension. METHODS: We examined the effects of low-frequency and low-intensity ultrasound (500 or 800kHz, 25mW/cm(2)) applied to the forearm on BP, pulse rate, and pulse pressure in 212 Japanese subjects (82 men and 130 women; mean age±SE, 65±1years) with type 2 diabetes and hypertension (systolic BP>140mmHg). The subjects were treated with anti-hypertension agents. RESULTS: Systolic and diastolic BP, pulse rate, pulse pressure in the 800-kHz ultrasound treatment group were significantly lower than the baseline values in hypertensive subjects with type 2 diabetes, and lower than those of placebo controls. In addition, systolic and diastolic BP, pulse rate, and pulse pressure in the 500-kHz ultrasound treatment group were significantly lower than the baseline values in hypertensive subjects with type 2 diabetes, and systolic BP, pulse rate, and pulse pressure were significantly lower than those of placebo controls. CONCLUSIONS: Low-frequency (800kHz or 500kHz) and low-intensity (25mW/cm(2)) ultrasound irradiation to the forearm might have potential usefulness as a therapeutic application for clinic hypertension in subjects with type 2 diabetes.

Analysis of the Japanese Diabetes Risk Score and fatty liver markers for incident diabetes in a Japanese cohort.

AIMS: We examined the effectiveness of the Japanese Diabetes Risk Score (JPDRISC) and fatty liver markers for predicting incident diabetes. METHODS: We created the JPDRISC. The study periods I and II were January 2007 to May 2009 and June 2009 to December 2011, respectively. A total of 2084 people (1389 men, 695 women; mean age: 46 years) were included. People with diabetes in the Period I and those with ethanol intake >140 g/week were excluded. A total of 1515 people were included. Fatty liver using ultrasonography scores (FLUS) were assigned. RESULTS: The mean observation period was 26.3 months, and 24 people had developed diabetes between the Periods I and II. In logistic regression analysis, the JPDRISC (OR=1.197, 95% C.I.: 1.062-1.350, p=0.003) and FLUS (OR=2.591, 95% C.I.: 1.411-4.758, p=0.002) in the Period I were independent determinants of incident diabetes. In receiver operating characteristic analysis, sensitivity and specificity for incident diabetes were 0.885 and 0.536, respectively, in people with both FLUS≥1 and the total JPDRISC≥6 in the Period I. The sensitivity was better than the JPDRISC alone (sensitivity 0.696) and FLUS alone (sensitivity 0.750). CONCLUSIONS: JPDRISC and FLUS were independently associated with incident diabetes and their combination is useful.

Fatty liver and serum cholinesterase are independently correlated with HbA1c levels: cross-sectional analysis of 5384 people.

OBJECTIVES: To examine the association between glycosylated haemoglobin (HbA1c) and fatty liver markers. METHODS: This cross-sectional analysis stratified subjects into quintiles based on HbA1c. Fatty liver using ultrasonography scores (FLUS) were assigned as follows: 2 points, moderate or severe fatty liver; 1 point, mild fatty liver; and 0 points, normal liver. Subjects with viral hepatitis, alcohol intake >175 g/week or receiving hypoglycaemic treatment were excluded. RESULTS: The study included 5384 subjects. Serum cholinesterase (ChE) and FLUS showed a significant graded increase with increasing HbA1c. In linear regression analysis stratified by body mass index (BMI) and age, ChE and FLUS were significantly associated with lower (1 + 2) and higher (3 + 4 + 5) HbA1c quintiles, respectively, independent of BMI and age. CONCLUSIONS: The findings show that both ChE and FLUS are significantly correlated with HbA1c, independent of BMI and age.

The diabetes-cardiovascular risk paradox: results from a Finnish population-based prospective study.

AIMS: To assess changes in coronary heart disease (CHD) event rates and CHD mortality rates among diabetic and non-diabetic individuals between two large study cohorts with baseline assessments 10 years apart and followed up for 10 years. METHODS AND RESULTS: Four population surveys were carried out in 1972, 1977, 1982, and 1987 in a randomly selected independent population in Finland. For the analyses, we combined the 1972 and 1977 cohorts (cohort 1) and similarly also the 1982 and 1987 cohorts (cohort 2). A total of 16 779 men and 18 235 women were followed up for 10 years. Whereas the risk of first cardiovascular disease event in women did not change between the two cohorts, the risk in diabetic men aged 25-49 years and men of all age groups with incidence diabetes during the follow-up decreased compared with the earlier cohort. The relative risk of CHD mortality in men with baseline diabetes or incident diabetes compared with non-diabetic individuals increased (from 1.67 to 1.75 and 1.00 to 1.92, respectively). CHD event rates and CHD mortality rates decreased among non-diabetic individuals between the two study cohorts. CONCLUSION: Special attention should be given to prevent the onset of diabetes in the population and to intensify the management of patients with diabetes.

The gender-specific impact of diabetes and myocardial infarction at baseline and during follow-up on mortality from all causes and coronary heart disease.

OBJECTIVES: The goal of this study is to compare the magnitude of diabetes and myocardial infarction (MI) at baseline and during follow-up on cause-specific and all-cause mortality. BACKGROUND: History of both MI and diabetes are strong predictors of coronary heart disease (CHD) death. However, gender-specific data on the joint effect of diabetes and MI, and particularly on the effect of incident diabetes and MI developed during the follow-up, on CHD mortality are scarce. METHODS: The baseline cohort study included 2,416 patients with prior diabetes or MI at baseline; the follow-up cohort study included 4,315 patients with incident diabetes or MI diagnosed during the follow-up. RESULTS: In the baseline cohort study, men with prior MI had a 20% to 80% increased risk of CHD or total mortality, but women with prior MI had a 43% to 45% decreased risk of CHD or total mortality in comparison with men and women with prior diabetes. In the follow-up cohort study, men and women with incident MI had a higher risk of CHD mortality (hazard ratio [HR] 2.15 in men and 1.65 in women), and an almost similar risk of total mortality (HR 0.95 in men and 1.02 in women) in comparison with men and women with incident diabetes. CONCLUSIONS: In men, MI at baseline or during follow-up confers a greater risk on CHD mortality than diabetes does. In women, prior MI at baseline confers a lower risk on CHD mortality than prior diabetes does, but incident MI during follow-up confers a greater risk than incident diabetes does. In both men and women, total mortality is similar for incident MI and diabetes.

Genetic and environmental effects on fasting and postchallenge plasma glucose and serum insulin values in Finnish twins.

The aim of this study was to evaluate genetic and environmental effects on plasma glucose, insulin secretion, and resistance in Finnish twins. Altogether 151 randomly selected twin pairs were examined by the oral glucose tolerance test; 66 twin pairs were monozygotic and 85 like-sexed dizygotic. We estimated the intraclass correlation coefficients and variance components of genetic and environmental effects on waist circumference, plasma glucose, and serum insulin. For fasting insulin, the proportion of total variation accounted for by additive genetic effects (A) and nonshared environmental effects (E) were 43 and 57%, respectively. As to postchallenge insulin and waist circumference, A effects were stronger in female twins (51 and 70%, respectively) than male twins in whom no significant evidence for genetic variance was found. Of the variation in fasting glucose, A and E effects accounted for 45 and 55%, respectively. Of the variation in postchallenge glucose, E effects had a greater role (65%), compared with A effects (35%); A effects on pre- and postchallenge insulin levels were highly correlated (genetic correlation coefficient = 0.81). In conclusion, additive genetic effects are important for the insulin secretion, whereas nonshared environmental effects contribute strongly to peripheral insulin resistance.

Population-based assessment of familial clustering of diabetic nephropathy in type 1 diabetes.

We determined the magnitude of familial aggregation in the development of diabetic nephropathy (DN) among a population-based cohort of Finnish type 1 diabetic patients. Probands with type 1 diabetes were identified from the nationwide register of all Finnish cases diagnosed during 1965-1979. By 1998, there were 537 families with at least two siblings with type 1 diabetes. These 537 probands and their 616 diabetic siblings were followed for a diagnosis of DN until the end of 2001. We identified 323 cases of DN in these families. If the proband had DN, 38% of the siblings also had DN, whereas out of the diabetic siblings of the probands without DN, only 17% had DN (P = 0.001). Diabetic siblings of the nephropathic probands had a 2.3 times (95% CI 1.4-2.7) higher risk of DN compared with siblings of probands free of DN. The presence of a severe form of DN in the proband increases the risk threefold for diabetic siblings. Sex, the DN of the proband, the age at the onset of diabetes, and parental type 2 diabetes were significant predictors of DN among diabetic siblings. Although the majority of sibpairs with type 1 diabetes are discordant for DN, its presence in one sibling doubles the risk for the other diabetic siblings.