Dyslipidemia in diabetes: a population-based study in Bali.

PURPOSE: To establish the lipid pattern in subjects with diabetes mellitus (DM) and factors that are correlated with insulin resistance and lipid disorders in a population of Bali. METHODS: A cross-sectional population-based study which enrolled 1840 subjects (age 13-100 years) from 7 villages was carried out. Several clinical parameters were measured including age, gender, body mass index, waist circumference (WC), fasting blood glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) A (apoA), apoB, non-HDL-C, T/HDL-C ratio, LDL-C/apoB ratio, apoB/A ratio, plasma insulin, and homeostasis of model assessment-insulin resistance (HOMA-IR). RESULTS: TC, TG, and non-HDL-C levels were higher in DM subjects than in normal glucose tolerance (NGT) subjects in both genders; total/HDL-C ratio was higher in subjects with DM than in NGT subjects only in men; LDL-C levels, apoB levels, and apoB/A ratios were higher and LDL/apoB was lower in subjects with DM than in NGT in women. In subjects with DM, the target for LDL-C (79%), non-HDL-C (85.2%), apoB (80%), HDL-C (34.9%), TG (46.7%), and small-dense low density lipoprotein (42.2%) was not achieved. CONCLUSION: FBG was correlated with TC, TG, LDL-C, apoB, non-HDL-C levels, LDL/apoB, and apoB/apoA ratios. Subjects with DM had higher levels of TC, TG, and non-HDL-C levels in both genders; T/HDL-C ratio only in men; LDL-C, apoB/apoA ratio and lower LDL/apoB ratio only in women. Obesity was correlated with lipid levels. WC was correlated with LDL/apoB ratio, insulin level, HOMA-IR, and TG; highest absolute strength of correlation was with LDL/apoB ratio. Insulin resistance was correlated with lipid levels or ratios, especially in women. In women, HOMA-IR had a positive correlation with total/HDL-C ratio, non-HDL-C, apoB, and a negative correlation with HDL-C levels.

Anti-hyperglycemic Effect of Long-Term Bis(hinokitiolato)zinc Complex ([Zn(hkt)2]) Ingestion on Insulin Resistance and Pancreatic Islet Cells Protection in Type 2 Diabetic KK-Ay Mice.

Zinc (Zn) is a trace element with anti-diabetes mellitus (anti-DM) effects. Zn complexes exhibit stronger insulin-like activity than Zn ions. Bis(hinokitiolato)zinc complex ([Zn(hkt)2]) was recently reported to be a potent anti-DM candidate. We examined the effects of [Zn(hkt)2] on insulin resistance and pancreatic islet cells through in vivo long-term ingestion studies. In an in vivo study, we performed 4-month long-term [Zn(hkt)2] administration experiments in KK-Ay mice as a type 2 DM animal model. Ingestion of [Zn(hkt)2] resulted in lower blood glucose levels compared with the non-treated KK-Ay mice (control group). Additionally, [Zn(hkt)2] treatment decreased plasma insulin concentration compared with that of the non-treated KK-Ay group. [Zn(hkt)2] treatment resulted in a significant suppression of islet cell enlargement and a significantly decreased number of insulin-positive cells compared with the non-treated KK-Ay control group. The [Zn(hkt)2] treatment group showed the increasing tendency in the amount of Zn levels in peripheral organs; liver, muscle, adipose, and pancreas, compared with the non-treated KK-Ay control group. However, the Zn level in the pancreas of the [Zn(hkt)2] treatment group did not show the significant increase compared with the non-treated KK-Ay control group. This accumulation of Zn in pancreas suggested that [Zn(hkt)2] mainly effects on the peripheral tissue, and [Zn(hkt)2] has the less effect on the pancreas directly. Thus, we concluded that [Zn(hkt)2] exerted the main effect on peripheral organs by ameliorating insulin resistance.

Isomeric effects of anti-diabetic α-lipoic acid with γ-cyclodextrin.

AIMS: Previous studies reported the anti-diabetic effects of α-lipoic acid (αLA) isomers: racemic-αLA, R-αLA, or S-αLA. Previously, we examined the anti-diabetic effects of αLA administered as a food additive, but were unable to demonstrate the differences among different isomers. In this study, αLAs were complexed with γ-cyclodextrin (γCD) for the stability.We then investigated the anti-diabetic effects of racemic-, R-, and S-αLA/γCDs in KKAy mice. MAIN METHODS: Male type 2 diabetic KKAy mice were divided into 5 groups, and fed either a high-fat-diet (HFD),HFD supplemented with γCD, or HFD supplemented with racemic-αLA/γCD, R-αLA/γCD, or S-αLA/γCD for 4 weeks. At the end of the feeding period, HbA1c and adiponectin levels were measured, PPARγ2mRNA expression levels were assessed in adipose tissues using real-time PCR, and AMP-activated protein kinase (AMPK) phosphorylation levels were evaluated in the liver by Western blotting. KEY FINDINGS: The anti-diabetic effects of αLA; the isomeric compounds racemic-, R-, and S-αLA/γCD were investigated using amale type 2 diabetic KKAy mousemodel. Significant differences were observed in HbA1c and plasma adiponectin levels between R-αLA/γCD-treated mice and control mice. PPARγ2 mRNA expression levels were slightly higher in racemic- and R-αLA/γCD-treated mice. Moreover, AMPK phosphorylation levels were elevated in racemic-αLA/γCD- and R-αLA/γCD-treated mice, but remained unchanged in S-αLA/γCD-treated mice. SIGNIFICANCE: These results suggested that the stereoisomerism mediates a difference in the anti-diabetic effects of racemic-, R-, and S-αLA/γCDs. Furthermore, the anti-diabetic mechanism of αLA/γCD action may be attributed to the activation of AMPK in the liver.

Antidiabetic effect of the α-lipoic acid γ-cyclodextrin complex.

In recent years, the number of patients suffering from diabetes mellitus has been increasing worldwide. In particular, type 2 diabetes mellitus, a lifestyle-related disease, is recognized as a serious disease with various complications. Many types of pharmaceutics or specific health foods have been used for the management of diabetes mellitus. At the same time, the relationship between diabetes mellitus and α-lipoic acid has been recognized for many years. In this study, we found that the α-lipoic acid γ-cyclodextrin complex exhibited an HbA1c lowering effect for treating type 2 diabetes mellitus in animal models. Moreover, in this study, we investigated the activation of phosphorylation of AMP-activated protein kinase, which plays a role in cellular energy homeostasis, in the liver of KKA(y) mice by using α-lipoic acid and the α-lipoic acid γ-cyclodextrin complex. Our results show that the α-lipoic acid γ-cyclodextrin complex strongly induced the phosphorylation of AMP-activated protein kinase. Thus, we concluded that intake of the α-lipoic acid γ-cyclodextrin complex exerted an antidiabetic effect by suppressing the elevation of postprandial hyperglycemia as well as doing exercise.

Underweight is an important risk factor for coronary heart disease in the population of Ceningan Island, Bali.

A study on the prevalence of coronary heart disease (CHD) and its risk factors in Ceningan Island was conducted. The prevalence of CHD was 11.5%. Older age (odds ratio, OR, 27.0), underweight (OR, 3.6), systolic hypertension (OR, 4.6), high total cholesterol (OR, 5.9), and high low-density lipoprotein cholesterol (OR, 3.1) were risk factors for a history of myocardial infarction (MI). By logistic regression analysis, only age (B=3.937) and underweight (B=1.275) consistently appeared to be risk factors for MI. The prevalence of CHD in the population was comparatively high.

Effects of Zn(II) complex with vitamins C and U, and carnitine on metabolic syndrome model rats.

The insulinomimetic activity of a Zn(ii) complex is reported. The effects of the Zn(ii) complex with ascorbic acid (Vitamin C; VC), methylmethionine sulfonium chloride (Vitamin U; VU) and l-carnitine were assessed in diet-induced metabolic syndrome model rats. Zn(VU)(2)Cl(2) and Zn(VC)Cl(2) were suggested to be useful supplementary materials for preventing metabolic syndrome by reducing visceral adipose tissues or accelerating blood fluidity.

Insulinomimetic Zn(II) complexes as evaluated by both glucose-uptake activity and inhibition of free fatty acids release in isolated rat adipocytes.

We prepared 4 new Zn(II) complexes with Zn(O4), Zn(N(2)O(2)), and Zn(S2O2) coordination modes and evaluated their insulinomimetic activities in an in vitro study. The insulinomimetic activities of bis(pyrrole-2-carboxylato)zinc (Zn(pc)2), bis(alpha-furonic acidato)zinc (Zn(fa)2), bis(thiophene-2-carboxylato)zinc (Zn(tc)2), and bis(thiophene-2-acetato)zinc (Zn(ta)2) complexes were found to be higher than that of zinc sulfate (ZnSO4). Zn(ta)2 showed the highest insulinomimetic activity among the Zn(II) complexes because of its high lipophilicity.

Increase of visceral fat area in Indonesians and Japanese with normal BMI.

We compared the visceral fat accumulation between Indonesians and Japanese. Non-obese (25>BMI> or =18.5) men aged between their 20s and 50s were collected in Toban including moderately populated middle-sized cities of Hyogo Prefecture in Japan, and Sangsit town and Pedawa village in Indonesia. Their visceral fat accumulation was assessed by determination of visceral fat area (VFA) that was measured through bio-electrical impedance analysis. VFA as well as VFA per body weight in those aged in their 20s did not vary significantly among Toban, Sangsit and Pedawa. In these three districts, they increased with age. Compared with VFA as well as VFA per body weight among those aged in their 20s, they increased in their 30s and over in the urban area of both Japan and Indonesia, whereas it did in their 40s and over in Pedawa, economically poor district. The inhabitants in their 40s and over in Sangsit and those in their 30s and over in Pedawa had less VFA than those with the corresponding age in Toban, while those in the 30s and 40s in Pedawa and those in their 40s in Sangsit had less VFA per body weight than those with corresponding age in Toban. In conclusion, the visceral fat appears to accumulate progressively with aging and urbanization of lifestyle even in those with normal body mass index. It is recommended that some preventive measures against visceral fat accumulation should be taken in their 20s or under for urban dwellers and in their 30s or under for rural inhabitants.

In vitro alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide.

We found alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide (6mpa-ma) which showed the highest blood glucose lowering effect in Zn(II) complexes with picolinamide derivatives in KK-A(y) mice. The Zn(II) complex showed strong alpha-glucosidase inhibitory activity greater by about eighty times (substrate: maltose) and forty times (substrate: sucrose) compared with acarbose.