Interaction between glycaemic control and serum insulin-like growth factor 1 on the risk of retinopathy in type 2 diabetes.

BACKGROUND: There is strong experimental evidence that insulin-like growth factor 1 (IGF-1) plays a role in the development of diabetic retinopathy. We carried out this study to determine the association between serum IGF-1 levels and retinopathy in patients with type 2 diabetes and whether this association is modified by the severity of hyperglycaemia. MATERIALS AND METHODS: A total of 480 consenting patients with type 2 diabetes were enrolled between 1 August 2001 and 31 December 2002. All participants provided a medical history and underwent a physical examination, biochemical assessment and eye fundi examination. These patients were followed up in our clinics according to our national guidelines until 31 December 2009. RESULTS: Compared with the middle tertile, increased levels of IGF-1 did not increase the risk of mild-to-moderate retinopathy (RR, 1·11; 95% CI, 0·63-1·95) and severe retinopathy (RR, 1·84; 95% CI, 0·79-8·57) at baseline. In the longitudinal analysis, increased levels of IGF-1 showed a nonsignificantly increased hazard ratio (HR) for the progression of retinopathy (HR, 1·61; 95% CI, 0·52-4·96) and severe retinopathy (HR, 1·63; 95% CI, 0·65-4·09). However, in patients with relatively good glycaemic control, there was a significantly increased risk of the progression of retinopathy (HR, 2·21; 95% CI, 1·01-5·91) and a cumulative incidence of severe retinopathy (HR, 4·82; 95% CI, 1·10-18·25) in individuals with the highest serum IGF-1 levels. CONCLUSIONS: Our data suggested serum IGF-1 was a contributing factor in severe diabetic retinopathy and this effect may be masked by poor glycaemic control.

Clinical and biochemical indicators of homeostasis model assessment-estimated insulin resistance in postmenopausal women.

BACKGROUND: Homeostasis model assessment of insulin resistance (HOMA-IR) is a surrogate estimate of directly measured insulin resistance that been robustly proven to be associated with diabetes and cardiovascular disease. The purpose of this study was to evaluate the use of several simple indicators to identify postmenopausal women with insulin resistance estimated by HOMA-IR. METHODS: We recruited 262 naturally postmenopausal women without overt diabetes for the study. HOMA-IR values were calculated from fasting glucose and insulin levels. Multiple linear regression analyses were carried out to detect determinants of HOMA-IR. Insulin resistance was conventionally defined as the upper quartile of the HOMA-IR values. The diagnostic power of clinical and biochemical markers for insulin resistance was assessed using receiver operating characteristic curves. RESULTS: Some 90% of the women with HOMA-IR ≥ 2.8 (75th percentile as cutoff) showed abnormal glucose metabolism and 45% of them had silent diabetes (odds ratio 6.09, 95% CI 3.17 - 11.73 vs. those with HOMA-IR < 2.8). Results revealed that uric acid, body mass index, waist circumference, alanine aminotransferase, triglycerides, and high-density lipoprotein cholesterol were important determinants of HOMA-IR in these women. Using uric acid ≥ 5.0 mg/dL as a cutoff point, we could diagnose insulin resistance with 75.4% sensitivity and 73.1% specificity. CONCLUSION: Postmenopausal women with HOMA-IR-estimated insulin resistance were at high risk of glucose abnormalities in this study. High HOMA-IR values were significantly associated with six clinical and biochemical indicators. Among these, high serum uric acid levels seemed to be a useful marker identifying postmenopausal women with insulin resistance. This study was registered at clinicaltrials.gov as NCT00945271.

Hemoglobin A(1c) and fructosamine for assessing glycemic control in diabetic patients with CKD stages 3 and 4.

BACKGROUND: Hemoglobin A(1c) (HbA(1c)) and fructosamine can be used to monitor glycemic control in diabetic patients with normal kidney function, but their validity in patients with chronic kidney disease (CKD) has not been evaluated. In this study, we evaluated the correlation and accuracy of these 2 measures of glycemic control in type 2 diabetic patients with CKD stages 3-4. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: Type 2 diabetic patients with normal (n = 30) and abnormal kidney function (n = 30) were recruited in Taipei Veterans General Hospital, Taiwan. INDEX TESTS: HbA(1c) and fructosamine. REFERENCE TEST: Self-monitoring of blood glucose levels. MEASUREMENTS: Blood glucose measurements consisted of 6 preprandial, 6 postprandial, and 2 bedtime assessments in a week with a cycle of 4-week intervals for 12 weeks. RESULTS: Correlation coefficients between HbA(1c) level or fructosamine-albumin ratio and mean blood glucose levels were 0.836 and 0.645 in participants with normal kidney function and 0.813 and 0.649 in participants with CKD stages 3-4, respectively. In patients with CKD stages 3-4, mean blood glucose levels in weeks 1-12 were 21.9 mg/dL (95% CI, 11.6-32.5) higher than estimated average glucose (eAG) levels calculated from HbA(1c) levels in participants with normal kidney function. In patients with CKD stages 3-4, mean blood glucose levels in weeks 10-12 were 15.5 mg/dL (95% CI, 5.2-30.5) higher than eAG levels calculated from fructosamine levels in participants with normal kidney function, but without statistical significance when eAG calculated from fructosamine level was corrected for serum albumin level (difference of 5.6 mg/dL; 95% CI, -8.6 to 19.8). LIMITATIONS: Relatively small number of participants with limited amount of blood glucose measurement data. CONCLUSION: Our data show that eAG calculated from HbA(1c) and fructosamine levels might underestimate mean blood glucose levels in patients with CKD stages 3-4. References ranges may need to be modified when interpreting results of measurements of glycemic control in type 2 diabetic patients with CKD.

Human SA gene polymorphisms are associated with non-high-density lipoprotein cholesterol in postmenopausal women: a pilot study.

OBJECTIVE: The purpose of the study is to evaluate the associations between polymorphisms of the human SA (SAH) gene, an acyl-CoA synthetase gene, with dyslipidemia and phenotypes of the insulin resistance syndrome in postmenopausal women. METHODS: One hundred and forty-two postmenopausal women were recruited for the study. Each subject received anthropometric and blood pressure measurements, fasting sampling for lipids, and a 75-g oral glucose tolerance test for insulin resistance. Genotypes of two polymorphisms in the promoter region (c.-962ins/del, c.-451G>A), one missense variant (c.1077G>C, p.K359N) in exon 8, and one in intron 12 (A>G) of the SAH gene, were determined. RESULTS: There were significant differences in genetic distribution of the SAH gene promoter I/D polymorphism between the two groups of subjects by non-high-density lipoprotein cholesterol (non-HDL-C) levels (p=0.004). The subjects with the DD genotype was associated with high levels of non-HDL-C (>160 mg/dL) as compared with the ID or II genotypes (p=0.002). Furthermore, three haplotypes were constructed based on the promoter I/D and the exon 8 G/C polymorphisms. Homozygosity for SAH haplotype 3 was associated with increased adiposity, insulin resistance, and elevated levels of non-HDL-C in the post menopausal women. The subjects with haplotype 3 had double the risk to have higher non-HDL-C levels than those with haplotype 1. CONCLUSION: Our results suggest that the polymorphisms of the SAH gene are associated with non-HDL-C levels in postmenopausal women. Further studies with larger sample sizes or different populations are warranted to confirm our preliminary findings.

Beneficial effects of insulin on glycemic control and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy.

OBJECTIVE: To evaluate whether treatment with insulin is advantageous compared with oral antidiabetes agents in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. RESEARCH DESIGN AND METHODS: Newly diagnosed type 2 diabetic patients with severe hyperglycemia were hospitalized and treated with intensive insulin injections for 10-14 days. The oral glucose tolerance test (OGTT) was performed after intensive insulin treatment. After discharge, the patients were randomized to receive either insulin injections or oral antidiabetes drugs (OADs) for further management. The OGTT was repeated 6 months later, and beta-cell function and insulin sensitivity were evaluated again. These subjects were continually followed up for another 6 months to evaluate their long-term glycemic control. RESULTS: At the 6th month of the study, the A1C level was significantly lower in the insulin group than in the OAD group (6.33 +/- 0.70% vs. 7.50 +/- 1.50%; P = 0.002). During the follow-up visit, the A1C level was still better in the insulin group (6.78 +/- 1.21% vs. 7.84 +/- 1.74%; P = 0.009). All parameters regarding beta-cell function measured in the OGTT were improved significantly in both groups after 6 months of treatment. Compared with the OAD group, the homeostasis model assessment of beta-cell function index, insulin area under the curve, and insulinogenic index were better in the insulin group. CONCLUSIONS: A 6-month course of insulin therapy, compared with OAD treatment, could more effectively achieve adequate glycemic control and significant improvement of beta-cell function in new-onset type 2 diabetic patients with severe hyperglycemia.

Fasting triglyceride is a major determinant of postprandial triglyceride response in postmenopausal women.

OBJECTIVE: The purpose of the study was to examine the relative influences of fasting lipids, insulin resistance, and waist circumference (WC) on postprandial lipemia in postmenopausal women. DESIGN: Forty-nine naturally postmenopausal women were recruited for the study. Each woman underwent a 75-g oral glucose tolerance test to measure insulin resistance and a 1,000-kcal high-fat mixed meal test for postprandial triglyceride (TG) response. RESULTS: The participants were divided into three groups by tertiles of incremental TG response in the mixed meal test. The three groups were comparable in weight, WC, and fasting high-density lipoprotein cholesterol (HDL-C) levels. There were significant differences in fasting TG and non-HDL-C concentrations among the three groups. The women in the high-tertile group were more insulin resistant than those in the low-tertile group, indicated by higher homeostasis model assessment for insulin resistance (HOMA-IR) values. The postprandial TG response was significantly correlated with Log(fasting TG), fasting non-HDL-C and Log(HOMA-IR), but not with WC, in univariate regression analyses. Log(fasting TG) was the only variable that remained significantly related to incremental TG response when all the above were entered into multiple regression models. Subsequently, we found that Log(HOMA-IR) and fasting non-HDL-C independently predicted the variance of Log(fasting TG) in stepwise multiple regression. CONCLUSIONS: Our data demonstrated that the fasting TG level is a major determinant of postprandial TG response in postmenopausal women. Insulin resistance and non-HDL-C may contribute independently to the fasting TG level. The influences of WC on postprandial lipemia seemed to be insignificant.

Is hyperuricemia another facet of the metabolic syndrome?

BACKGROUND: Hyperuricemia is commonly associated with obesity, glucose intolerance, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. The resemblance of the metabolic syndrome and hyperuricemia has led to the suggestion that hyperuricemia is a part of the metabolic syndrome. The purpose of this study is to examine the contribution of uric acid (UA) as an additional component of the metabolic syndrome in middle-aged men. METHODS: In total, 393 male participants, aged 45-60 years, were recruited from a professional health evaluation program. Anthropometric measurements and blood pressure (BP) were taken after an overnight fast. Fasting blood samples were collected for the measurements of glucose, UA, and lipid profile. Logistic regression models were fitted to examine the relationship between UA and the diagnosis of metabolic syndrome. Factor analysis was performed to explore the relationship between UA and the components of the metabolic syndrome. RESULTS: The diagnosis of the metabolic syndrome was significantly associated with waist circumference (WC), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), systolic BP, and liver enzyme levels, but not associated with UA levels. The sensitivity of hyperuricemia (serum UA > or = 7.0 mg/dL) for the diagnosis of the metabolic syndrome was 58.0% and the specificity was 55.3%. In factor analysis, UA aggregated with body mass index, WC, glucose, log TG, and HDL-C as a metabolic factor. Systolic and diastolic BP were loaded on a second factor separately. The model loaded with UA explained a similar proportion of the total variance (56.9%), as did the model loaded without UA (62.5%). CONCLUSION: Our results suggest that the contribution of UA as an additional component of the syndrome seems to be insignificant. We propose that hyperuricemia might not be an important facet for the understanding of the underlying structure of the metabolic syndrome.

Waist circumference predicts metabolic cardiovascular risk in postmenopausal Chinese women.

OBJECTIVE: The purpose of the study is to compare the differences in metabolic cardiovascular risk factors among postmenopausal Chinese women with or without abdominal obesity. DESIGN: The study is a cross-sectional, population-based, comparative cohort study. Each participant received anthropometric measurements and a 75-g oral glucose tolerance test after an overnight fast. The homeostasis model assessment for insulin resistance and the insulin sensitivity index, ISI, were used as measures of insulin resistance. A "metabolic cardiovascular risk score" was calculated from fasting insulin, glucose, lipids, and blood pressure. General linear models (GLM) were fit to examine the relation of waist circumference (WC) to insulin resistance and metabolic risk scores.(0,120). RESULTS: According to the International Obesity Task Force obesity criteria for Asians, 57 women had abdominal obesity (WC >/= 80 cm), and 58 had WCs less than 80 cm. The two groups were comparable in demographic variables and body mass index (BMI). The women with larger WCs were more insulin-resistant than their counterparts. The metabolic risk scores were significantly higher in women with abdominal obesity than in those without it. The results from the GLM showed that WC was an independent predictor of insulin resistance and metabolic risk scores after controlling for demographic variables (0.06- and 0.29-unit increases in homeostasis model assessment for insulin resistance and metabolic risk scores per 1 cm change in WC). Moreover, BMI neither correlated with metabolic risk scores nor affected the WC effects on insulin resistance and metabolic risk scores in the GLM. CONCLUSIONS: Postmenopausal Chinese women with abdominal obesity may carry higher metabolic cardiovascular risk than those without it. It is WC, not BMI, that predicts metabolic cardiovascular risk factors in these women.

Portable electrochemical blood uric acid meter.

We describe a new portable uric acid (UA) meter, called the UASure (Apex Biotechnology Corp., Hsinchu, Taiwan). The UASure is an electrochemical blood UA meter designed for fast monitoring of UA concentrations in one drop of capillary blood using an electrochemical test strip. We compared the UASure with the standard method, the Hitachi 7600 modular system (Hitachi, Tokyo, Japan), in 146 volunteers (average age 62.5 +/- 12.8 years). Of these, 65 were known hyperuricemic subjects, 17 of whom received medical therapy. The patients donated their capillary and venous blood samples in random order. Capillary blood and one drop of venous blood were tested immediately by the UASure. The venous blood in the test tube was sent to the central laboratory for serum UA measurement by the Hitachi 7600. The intra-assay coefficients of variation (CVs) of the UASure were 4.79%, 5.77%, and 3.08% at UA levels of 5.8, 7.1, and 13.5 mg/dl, respectively. The UA concentrations tested by the UASure correlated well with those by the Hitachi 7600 (r = 0.87 in venous sampling and r = 0.78 in capillary sampling, P < 0.001). The intraclass correlation was good for venous samples by the UASure (rI = 0.84, 95% CI 0.82-0.90), somewhat below the meaningful criterion for capillary samples by the UASure (rI = 0.77, 95% CI 0.69-0.83). UASure with venous sampling is interchangeable with the standard method for UA measurement.