R. P. Narayanan

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 (β=−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.

Interactions of the IGF System with Diabetes and its Vascular Complications.

The insulin-like growth factor (IGF) system is an evolutionarily conserved group of important proteins that are fundamental to life. Indeed, insulin can be viewed as simply a specialized arm of the IGF system that has evolved to regulate primarily metabolic functions. The main purpose of the IGF system is to form a highly refined mechanism for the control of cellular growth, metabolism and survival. Dysregulation of such a system can have serious consequences. In this review we have focussed on the IGF system and its relation to diabetes and the development of cardiometabolic disorders.

Fit for Birth - the effect of weight changes in obese pregnant women on maternal and neonatal outcomes: a pilot prospective cohort study.

The ‘Fit for Birth’ study aimed to explore patterns of gestational weight gain and their relationship with pregnancy outcomes.

Socioeconomic deprivation independently predicts painful diabetic neuropathy in type 2 diabetes.

OBJECTIVE Painful peripheral neuropathy in people with type 2 diabetes is a disabling complication. We explored associations of this condition with socioeconomic deprivation. RESEARCH DESIGN AND METHODS The Townsend index of socioeconomic deprivation was examined in the pseudonymised GP records of 15388 (44.1% female) individuals with type 2 diabetes in the Cheshire county of England, and related to prevalence of drug treated painful diabetic neuropathy. We also analysed prescription trends with respect to pharmacotherapy for neuropathy pain relief. RESULTS Treatment for neuropathic pain was initiated in 3 266 (21.2%) of patients. Those on treatment were older [68.2 (95% CI 67.8-68.7) vs. 66.6 (66.4-66.8) years] than those not on treatment. There was no difference in HbA1c (7%, 55 mmol/mol).There were significant differences between the groups for the Townsend deprivation index, with a greater proportion (30.6% vs. 22.8% of patients with treated neuropathic pain) having a score of ≥1 (Χ(2)=83.9, p<0.0001).Multivariate logistic regression analyses indicated that each unit increment in the Townsend index was associated with an 6% increased odds of requiring neuropathic pain treatment [odds ratio (95%CI) 1.06 (1.05-1.08), p<0.0001] independent of 5 year age band, BMI, gender, systolic BP, eGFR, HbA1C and total cholesterol. CONCLUSIONS In this study using pseudonymised clinical records, a higher level of socioeconomic deprivation seemingly may predispose to severe neuropathic pain in diabetes requiring pharmacological intervention. Targeted allocation of healthcare resources to this group may offer clinical benefits.

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.

Evaluation of Aintree LOSS, a community‐based, multidisciplinary weight management service: outcomes and predictors of engagement

Aintree LOSS is a community‐based, multidisciplinary weight management programme for patients with severe and complex obesity, focusing on a flexible and individualized service with follow‐up for up to 2 years. We evaluated all 2472 patients referred to the service between October 2009 and 2013. Demographic data were recorded at baseline, with the Index of Multiple Deprivation (IMD) used to measure socioeconomic deprivation. Weight was recorded at each visit. Mean body mass index at baseline was 45.6 (standard deviation 6.8), and 58.9% of patients lived in areas in the most deprived decile nationally. Of 2315 appropriate referrals, 1249 (55.1%) attended >2 visits; mean final weight loss was 3.50 ± 8.55 kg, and 24.1% achieved ≥5% weight loss. Of the patients, 754 (33.3%) attended for over 6 months; mean final weight loss was 4.94 ± 10 kg, and 34% achieved 5% weight loss. Multivariate logistic regression analysis showed increasing age, residence in a less deprived area and sleep apnoea to be independently associated with attendance for >6 months, and there was a linear relationship between 6‐month attendance and deprivation quintile. Year‐on‐year analyses showed improvement in engagement over time, coinciding with efforts to improve access to the service. This work shows a multidisciplinary, community‐based weight loss programme prioritizing a fully flexible and individualized approach functioning effectively in real‐world practice. Maintaining engagement remains a challenge in weight loss programmes, and our results suggest younger patients living in areas with greater deprivation should be a target for efforts to improve engagement.

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

Abstract 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 β = 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.

Screening methods for obstructive sleep apnoea in severely obese pregnant women

Obstructive sleep apnoea (OSA) is an often‐overlooked diagnosis, more prevalent in the obese population. Screening method accuracy, uptake and hence diagnosis is variable. There is limited data available regarding the obese pregnant population; however, many studies highlight potential risks of apnoeic episodes to mother and foetus, including hypertension, diabetes and preeclampsia. A total of 162 women with a body mass index (BMI) ≥ 35 were recruited from a tertiary referral hospital in the northwest of England. They were invited to attend three research antenatal clinics, completing an Epworth Sleepiness Scale (ESS) questionnaire at each visit. A monitor measuring the apnoea hypopnoea index (AHI) was offered at the second visit. Data taken from consent forms, hospital notes and hospital computer records were collated and anonymized prior to statistical analysis. A total of 12.1% of women had an ESS score of >10, suggesting possible OSA. Rates increased throughout pregnancy, although unfortunately, the attrition rate was high; 29.0% of women used the RUSleeping (RUS) meter, and only one (2.1%) met pre‐specified criteria for OSA (AHI ≥ 15). This individual had OSA categorized as severe and underwent investigations for preeclampsia, eventually delivering by emergency caesarean section due to foetal distress. The accuracy of the ESS questionnaire, particularly the RUS monitor, to screen for OSA in the pregnant population remains unclear. Further research on a larger sample size using more user‐friendly technology to confidently measure AHI would be beneficial. There are currently no guidelines regarding screening for OSA in the obese pregnant population, yet risks to both mother and foetus are well researched.

Are cholesterol levels being checked and managed appropriately in UK primary care type 2 diabetes

Nutrition and your health: dietary guidelines for Americans. www.health.gov/dietaryguidelines/dga2005/report/HTML/E_translation.htm (accessed May 29, 2015) 10 Inge TH, Garcia V, Daniels S et al. A multidisciplinary approach to the adolescent bariatric surgical patient. J Pediatr Surg 2004; 39: 442–7. 11 Ference BA, Yoo W, Alesh I et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol 2012; 60: 2631–9. Disclosure