BMI independently relates to glycaemia in patients with severe enduring mental illness (SMI).

BACKGROUND: People with severe mental illness (SMI) have higher rates of diabetes than the general population. AIMS: To assess the type-2 diabetes screening rates in primary care and the relation between body mass index (BMI) and dysglycaemia for patients on the SMI register in the Cheshire region of the United Kingdom. METHODS: The setting was 24 general practices in Central and Eastern Cheshire, United Kingdom. Subjects were identified through a semianonymized search of GP registers. RESULTS: About 451 of the 787 SMI patients were screened for dysglycaemia and dyslipidaemia. Fasting glucose was in the impaired fasting glycaemia range (6.1-6.9 mmol/l) in 6.5%, and indicative of type-2 diabetes (≥7.0 mmol/l) in 17.3%. There was a positive univariate relation between BMI and fasting glucose (normalized ß = 0.26, p < 0.001). In multivariate models, adjusting for age, gender, smoking and blood pressure, each unit increase in BMI [OR = 1.07 (1.01, 1.13); p = 0.031] and triglycerides [OR = 1.28 (1.06, 1.55); p = 0.009] were independently associated with an increased risk of having type-2 diabetes. CONCLUSION: Increasing BMI relates to dysglycaemia in patients with severe enduring mental illness (SMI). All patients with SMI whether or not receiving neuroleptic treatment should undergo routine monitoring of weight and metabolic parameters.

Insulin-like growth factor-II and insulin-like growth factor binding protein-2 prospectively predict longitudinal elevation of HDL-cholesterol in type 2 diabetes.

INTRODUCTION: Associations of insulin-like growth factor-II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) with cardiovascular risk have been inadequately studied. We hypothesized that IGF-II and IGFBP-2 associate with longitudinal trends in lipid profiles in type 2 diabetes patients. SUBJECTS AND METHODS: Four hundred and eighty nine subjects with type 2 diabetes (age 27-87 years) from the Salford Diabetes Cohort were studied. Longitudinal clinical information was extracted for an eight-year period (2002-2009) from an integrated electronic dataset of primary care and hospital data. RESULTS: There were 294 male subjects and mean age was 62.9 years. At baseline, IGF-II concentration was 602 ng/mL. HDL cholesterol at baseline was associated with log-IGF-II concentration in a model adjusted for age, gender, baseline body-mass index (BMI), estimated glomerular filtration rate (eGFR) and lipid-lowering therapy. IGFBP-1 and IGFBP-2 were associated with high HDL-cholesterol. A higher circulating IGF-II concentration at baseline was also associated with longitudinal increase in HDL-cholesterol in mixed-effects regression analyses independent of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, age, gender, eGFR, BMI and lipid-lowering therapy. Log-transformed baseline concentrations of IGFBP-1 and IGFBP-2 were also associated with longitudinal elevation in HDL-cholesterol. No association was observed for IGF-II or IGFBP-2 with longitudinal LDL cholesterol trends. CONCLUSION: Our analyses based on 'real world' data demonstrate that higher baseline IGF-II and IGFBP-2 predict increased HDL concentration over time, implicating IGF-II in modulation of circulating HDL-cholesterol concentrations.

Atorvastatin administration is associated with dose-related changes in IGF bioavailability.

OBJECTIVE: IGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins. DESIGN AND METHODS: We measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (S.D.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg). RESULTS: Atorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: -3 (-21 to 14) ng/ml; IGF2: -23 (-65 to 18) ng/ml and IGFBP3: -0.34 (-0.71 to 0.03) µg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant -0.41 (-0.69 to 0.13, P=0.004). CONCLUSION: IGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.

IGFBP2 is a biomarker for predicting longitudinal deterioration in renal function in type 2 diabetes.

OBJECTIVE: Insulin-like growth factors are implicated in the development of diabetic nephropathy. IGF-binding protein 2 (IGFBP2) and IGF2 are expressed in the kidney, but their associations with diabetic nephropathy are unclear. We therefore tested the hypothesis that circulating levels of IGF2 and IGFBP2 predict longitudinal renal function in individuals with type 2 diabetes. DESIGN AND METHODS: IGFBP2 and IGF2 measurements were performed in 436 individuals (263 males) with type 2 diabetes. Linear mixed-effect regression analysis was used to model the relationship between plasma IGFBP2 concentration and longitudinal changes in estimated glomerular filtration rate (eGFR) over an 8-year period. Analyses were also performed for IGF1, IGF2, IGFBP1 and IGFBP3 concentrations as predictors of longitudinal renal outcomes. RESULTS: High IGFBP2 concentration at baseline was associated with a decreased eGFR over an 8-year period (ß=-0.02, (95% confidence interval -0.03 to -0.01), P<0.001). High IGFBP1, IGFBP2 and IGFBP3 were also associated with low baseline eGFR concentration. CONCLUSION: This study demonstrates that IGFBP2 is a predictor of longitudinal deterioration of renal function in type 2 diabetes.

Type 1 diabetes in Cheshire: cardiometabolic risk factor trends (2004-2009).

AIMS: In the context of changes in the last 10 years in treatment strategies for type 1 diabetes we evaluated longitudinal trends in cardiometabolic risk factor profiles in a population from North-West England. METHODS: We retrospectively examined longitudinal case records for the period for 291 adult patients followed up between 2004 and 2009 (age range 16-85). Data search was performed through the EMIS® software provider using data held in primary care. RESULTS: Longitudinal analysis of individually followed patients indicated a mean 0.4% reduction in HbA1c from 8.3% (67 mmol/mol) at baseline (p=0.002). The proportion of patients with an HbA1c ≥10% (86 mmol/mol) at baseline had a significant reduction over time from 14.0% to 9.5% (χ(2)=9.4, p=0.002). BMI remained unchanged (28.3 vs 28.4 kg/m(2)). However total cholesterol fell by 12.5% from 4.8mM to 4.2mM, (p<0.0001) with a corresponding 23% reduction in LDL-cholesterol from 3.0mm to 2.3mM (p<0.0001). There was a significant fall in diastolic BP (78-74 mmHg, p=0.0016). In a mixed longitudinal regression model, HbA1c was associated with LDL-C (ß=0.28, p<0.001) and age (ß=0.02, p=0.001), independent of BMI, gender and systolic BP. DISCUSSION: In spite of intensive work to improve glycaemic control in type 1 diabetes, mean HbA1c remains above target for many people in our area, highlighting the difficulty of achieving glycaemic targets in type 1 diabetes. The significant reduction in diastolic BP, LDL and total cholesterol may have long-term benefit in cardiovascular event rate reduction.