Baseline Circulating FGF21 Concentrations and Increase after Fenofibrate Treatment Predict More Rapid Glycemic Progression in Type 2 Diabetes: Results from the FIELD Study.

BACKGROUND: It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of ß-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. RESULTS: Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). CONCLUSIONS: Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function.

Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year. METHODS AND FINDINGS: In this study, 573 women were randomised to either the intervention (n = 284) or usual care (n = 289). At baseline, 10% had impaired glucose tolerance and 2% impaired fasting glucose. The diabetes prevention intervention comprised one individual session, five group sessions, and two telephone sessions. Primary outcomes were changes in diabetes risk factors (weight, waist circumference, and fasting blood glucose), and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors. The mean changes (intention-to-treat [ITT] analysis) over 12 mo were as follows: -0.23 kg body weight in intervention group (95% CI -0.89, 0.43) compared with +0.72 kg in usual care group (95% CI 0.09, 1.35) (change difference -0.95 kg, 95% CI -1.87, -0.04; group by treatment interaction p = 0.04); -2.24 cm waist measurement in intervention group (95% CI -3.01, -1.42) compared with -1.74 cm in usual care group (95% CI -2.52, -0.96) (change difference -0.50 cm, 95% CI -1.63, 0.63; group by treatment interaction p = 0.389); and +0.18 mmol/l fasting blood glucose in intervention group (95% CI 0.11, 0.24) compared with +0.22 mmol/l in usual care group (95% CI 0.16, 0.29) (change difference -0.05 mmol/l, 95% CI -0.14, 0.05; group by treatment interaction p = 0.331). Only 10% of women attended all sessions, 53% attended one individual and at least one group session, and 34% attended no sessions. Loss to follow-up was 27% and 21% for the intervention and control groups, respectively, primarily due to subsequent pregnancies. Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline. CONCLUSIONS: Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk, the level of engagement during the first postnatal year was low. Further research is needed to improve engagement, including participant involvement in study design; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000338066.

Clinical outcomes associated with albuminuria in central Australia: a cohort study.

BACKGROUND: Chronic kidney disease (CKD) and end-stage-kidney disease (ESKD) continue to be under-diagnosed and a major burden for Aboriginal communities in central Australia. The aim of this study was to examine the risk of poor clinical outcomes associated with elevated albumin-to-creatinine ratio (ACR) among Aboriginal people in central Australia. METHODS: Cox proportional hazards models were used to estimate the risk of end stage kidney disease (ESKD), dialysis, CVD (cardiovascular disease) and mortality associated with participants' baseline albuminuria reading from a 10-year cohort study of Aboriginal people (n = 623) from three communities in central Australia. Predictors of progression of albuminuria were also examined in the context of the Kidney Health Australia (KHA) Risk Matrix. RESULTS: A baseline ACR level of ≥3.5 mg/mmol was associated with an almost 10-fold increased risk of ESKD (95%CI 2.07-43.8) and a 15-fold risk of dialysis (95%CI 1.89-121). Albuminuria ≥3.5 mg/mmol was also associated with a borderline 63 % increased risk of CVD (95%CI 0.98-2.71). No significant association was observed with mortality from all-causes or chronic disease. Diabetes and a waist-to-hip ratio ≥0.90 independently predicted a two-fold increased risk of a progression to higher ACR levels. CONCLUSIONS: A single measure of moderately increased albuminuria was a strong predictor of renal failure in this population. A single spot urine ACR analysis in conjunction with the KHA Risk Matrix may be a useful and efficient strategy to screen for risk of CKD and progression to dialysis in remote communities. A focus on individuals with diabetes and/or central obesity for strategies to avoid increases in albuminuria may also prevent future CKD and CVD complications.

Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses. METHODS: Women (n = 3,657) and men (n = 6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex. RESULTS: Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p < 0.001). Fenofibrate reduced total, LDL- and non-HDL cholesterol and apolipoprotein B more in women (all p < 0.001), independent of menopausal status and statin uptake. Adjusted for covariates, fenofibrate reduced total cardiovascular outcomes (cardiovascular death, fatal and non-fatal stroke and carotid and coronary revascularisation) by 30% in women (95% CI 8%, 46%; p = 0.008) and 13% in men (95% CI -1%, 24%; p = 0.07) with no treatment-by-sex interaction (p > 0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI -7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p > 0.1). CONCLUSIONS/INTERPRETATION: Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.

An exploratory trial of insulin initiation and titration among patients with type 2 diabetes in the primary care setting with retrospective continuous glucose monitoring as an adjunct: INITIATION study protocol.

BACKGROUND: Insulin initiation and titration in primary care is necessary to respond to the growing epidemic of type 2 diabetes (T2D). The INITIATION study aims to evaluate the impact of implementing a new model of care with Primary Care Physician and Practice Nurse (PN) teams supported by a Credentialed Diabetes Educator-Registered Nurse (CDE-RN) and endocrinologist in initiating and titrating basal and prandial insulin for T2D patients in the Australian healthcare system over 24 weeks. This study also explores the feasibility and efficacy of retrospective continuous glucose monitoring (r-CGM) in comparison with self-monitoring of blood glucose (SMBG) among people with T2D in primary care. METHODS/DESIGN: The study employs a before and after design with a nested exploratory trial of SMBG and r-CGM. A total of 102 insulin naïve T2D patients with a glycated haemoglobin (HbA1c) level of >7.5% in the previous 6 months while treated with maximal oral therapy will be recruited and screened from 22 primary care practices in Melbourne, Australia. All patients will be commenced on a basal insulin regimen following randomization into one of the two blood glucose monitoring arms, with intensification to a "basal plus" regimen if required. The outcomes of the new model of care will be benchmarked with data collected over the same period from a specialist setting in Melbourne, Australia. DISCUSSION: This article describes the study protocol and insulin treatment algorithm employed in the first study to explore r-CGM use among T2D in primary care. Findings from the INITIATION study will inform development of a larger randomized controlled trial. TRIAL REGISTRATION: ACTRN12610000797077.

Relationship of low molecular weight fluorophore levels with clinical factors and fenofibrate effects in adults with type 2 diabetes.

People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04-0.16, all p < 0.01). Independent determinants of LMW-F included smoking, diastolic blood pressure, prior cardiovascular disease or microvascular complications, Caucasian ethnicity, kidney function, HbA1c and diabetes duration (all p ≤ 0.01). Baseline LMW-F tertiles correlated with on-trial macrovascular and microvascular complications (trend p < 0.001) on univariate analyses only. Six weeks of fenofibrate increased LMW-F levels by 21% (p < 0.001). In conclusion, LMW-F levels correlate with many risk factors and chronic diabetes complications, and are increased with fenofibrate. LMW-F tertiles predict complications, but not independently of traditional risk factors.

Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial.

BACKGROUND: Amputations in people with type 2 diabetes mellitus substantially impair their quality of life and impose high costs on health-care systems. Our aim was to assess the effect of fenofibrate on amputation events in a large cohort of patients with type 2 diabetes. METHODS: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 9795 patients aged 50-75 years with type 2 diabetes were randomly assigned by computer-generated randomisation sequence to receive fenofibrate 200 mg per day (n=4895) or matching placebo (n=4900) for 5 years' duration. Information about non-traumatic amputation-a prespecified tertiary endpoint of the study-was routinely gathered. Clinicians who were masked to treatment allocation adjudicated amputations as minor or major (below or above the ankle, respectively). Amputations were also classified on the basis of whether or not large-vessel disease was present in the limb, to distinguish those related to large-artery atherosclerosis from those predominantly related to microvascular disease. Analysis was by intention to treat (ITT). The FIELD study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481. FINDINGS: All 9795 patients were included in the ITT population. 115 patients had one or more non-traumatic lower-limb amputations due to diabetes. Previous cardiovascular disease, microvascular disease, previous non-traumatic amputation or skin ulcer, smoking, and longer duration of diabetes were more frequent in patients who had amputations during the trial than in those who had other cardiovascular events or in those who had neither event (all p<0.001 for three-way comparison). Mean lipid concentrations differed between patients who had on-study amputations and those who had other cardiovascular events or neither event, but by no more than 0.2 mmol/L. The risks of first amputation (45 vs 70 events; hazard ratio [HR] 0.64, 95% CI 0.44-0.94; p=0.02) and minor amputation events without known large-vessel disease (18 vs 34 events; 0.53, 0.30-0.94; p=0.027) were lower for patients assigned to fenofibrate than for patients assigned to placebo, with no difference between groups in risk of major amputations (24 vs 26 events; 0.93, 0.53-1.62; p=0.79). INTERPRETATION: Classic markers of macrovascular and microvascular risk were associated with lower extremity amputations in patients with type 2 diabetes. Treatment with fenofibrate was associated with a lower risk of amputations, particularly minor amputations without known large-vessel disease, probably through non-lipid mechanisms. These findings could lead to a change in standard treatment for the prevention of diabetes-related lower-limb amputations. FUNDING: Laboratoires Fournier SA (now part of Solvay Pharmaceuticals) and National Health and Medical Research Council of Australia.

C-reactive protein concentrations are very high and more stable over time than the traditional vascular risk factors total cholesterol and systolic blood pressure in an Australian aboriginal cohort.

BACKGROUND: Stability of circulating high-sensitivity C-reactive protein (hsCRP) concentrations has implications for its utility in assessing cardiovascular disease (CVD) risk. We sought to determine hsCRP reproducibility in an indigenous Australian cohort with a view to use hsCRP as a marker of future CVD in community-based risk-factor screenings. METHODS: Seventy people living in a community on the northern coast of Australia participated in 2 risk-factor screenings over a median (interquartile range) follow-up time of 829 (814-1001) days. hsCRP was measured by high-sensitivity nephelometry. RESULTS: Geometric mean hsCRP concentrations at baseline and follow-up were 4.5 and 5.1 mg/L, respectively (P = 0.220), and Pearson product-moment correlation was 0.775. The proportion of people at high CVD risk (hsCRP >3.0 mg/L) at baseline was 67.1% and remained consistently high (68.6%) at follow-up. Linear regression analysis for follow-up hsCRP as a function of baseline hsCRP, sex, and differences in total and regional body fatness showed that baseline hsCRP was the single predictor in the model, accounting for 63.9% of the total variance in follow-up hsCRP (P(model) < 0.001). Prevalence agreement (95% CI) between baseline and follow-up for the hsCRP >3.0 mg/L category was 84% (73%-92%) (P(McNemar) = not significant), and kappa coefficient was fair (0.64, compared with 0.31 for systolic blood pressure > or =140 mmHg and 0.43 for total cholesterol > or =5.5 mmol/L). CONCLUSIONS: hsCRP concentrations remained consistently reproducible over time across a wide concentration range in an Aboriginal cohort. Correlations between concentrations over time were better than for other traditional CVD risk factors. hsCRP concentration has potential as a marker of future CVD risk.

Increased coated-platelet levels in chronic haemodialysis patients.

AIM: To determine if levels of coated-platelets, which are potentially pro-thrombotic, are increased in end-stage renal disease patients on haemodialysis, a condition associated with high cardiovascular disease risk. METHODS: In a cross-sectional observational study, coated-platelet levels were measured by flow cytometry in 25 end-stage renal failure haemodialysis patients and 25 controls without renal disease. Associations between coated-platelet levels and clinical and biochemical factors relevant to renal and cardiovascular disease were evaluated. RESULTS: Mean +/- SD coated-platelet levels were higher in the dialysis group than in the control group (39.3+/-14.3% vs 30.9+/-10.3%, P=0.02). The number of subjects with high coated-platelet levels (>40%) was larger in the dialysis than in the control group (13/25 vs 4/25, chi(2) test, P=0.007). On univariate analysis, coated-platelet levels correlated with serum C-reactive protein levels in renal failure (r=0.47, P=0.02) and inversely with white cell count in the control group (r= -0.60, P=0.001). Coated-platelet levels were higher in dialysis patients reporting alcohol abstinence than among those reporting 'social' drinking (44.3+/-12.6 vs 28.8+/-13.5%, P=0.01). Age, gender, body weight, smoking, diabetes, lipid levels and lipid-lowering drugs were not associated with coated-platelet levels (all P>0.05). CONCLUSION: Coated-platelet levels are increased in haemodialysis patients relative to subjects with normal renal function, and are related to inflammation and alcohol abstinence. Other vascular risk factors, such as smoking, lipids and diabetes, were not related to coated-platelet levels. Coated-platelets may be implicated in the increased thrombosis and vascular risk in end-stage renal disease.

The COACH program produces sustained improvements in cardiovascular risk factors and adherence to recommended medications-two years follow-up.

PURPOSE: To assess whether The COACH Program could sustain its favourable impact on coronary risk factors (CRFs) and adherence to recommended medication for 18 months after the completion of The COACH Program. METHOD: A clinical audit of a secondary prevention program performed in three teaching hospitals in Melbourne, Victoria for patients with coronary heart disease (CHD). The CRF targets were based on recommendations from the National Heart Foundation of Australia between 2003 and 2007. RESULTS: 656 patients were followed by telephone every 6 months from recruitment in hospital for 2 years. There was a substantial improvement in all CRF from discharge from hospital to the completion of active coaching 6 months after hospital discharge. There was also a significant increase in the proportion of patients taking statins and renin-angiotensin system antagonists in the same period of time. There was a small deterioration in CRF status in the 6 months after exit from The COACH Program but thereafter CRF status was maintained and substantially better than that on entry to The COACH Program. The use of the recommended cardio-protective medications remained at the levels achieved at exit from The COACH Program. CONCLUSION: The changes in CRF status and adherence to cardiac medications achieved at 6 months in The COACH Program are sustained for at least 18 months after cessation of The COACH Program.

Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus.

OBJECTIVES: Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. METHODS: Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/-15 months). LMW-F levels were also measured once in 112 healthy control subjects. RESULTS: Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml respectively vs. 3.8+/-2.1 AU/ml; p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml; p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). CONCLUSIONS: LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.

Transient epigenomic changes during pregnancy and early postpartum in women with and without type 2 diabetes.

AIM: To investigate epigenomic changes in pregnancy and early postpartum in women with and without type 2 diabetes. METHODS: Dimethylation of histones H3K4, H3K9, H3K27, H3K36 and H3K79 was measured in white blood cells of women at 30 weeks pregnancy, at 8-10 and 20 weeks postpartum and in never-pregnant women. RESULTS: Dimethylation levels of all five histones were different between women in pregnancy and early postpartum compared with never-pregnant women and were different between women with and without type 2 diabetes. CONCLUSION: Histone methylation changes are transient in pregnancy and early postpartum and may represent normal physiological responses to hormones. Different epigenomic profiles in women with type 2 diabetes mellitus may correlate with hormonal responses, leading to high risk pregnancy outcomes.

Results of the first recorded evaluation of a national gestational diabetes mellitus register: Challenges in screening, registration, and follow-up for diabetes risk.

OBJECTIVE: Gestational Diabetes Mellitus (GDM) increases the risk of type 2 diabetes. A register can be used to follow-up high risk women for early intervention to prevent progression to type 2 diabetes. We evaluate the performance of the world's first national gestational diabetes register. RESEARCH DESIGN AND METHODS: Observational study that used data linkage to merge: (1) pathology data from the Australian states of Victoria (VIC) and South Australia (SA); (2) birth records from the Consultative Council on Obstetric and Paediatric Mortality and Morbidity (CCOPMM, VIC) and the South Australian Perinatal Statistics Collection (SAPSC, SA); (3) GDM and type 2 diabetes register data from the National Gestational Diabetes Register (NGDR). All pregnancies registered on CCOPMM and SAPSC for 2012 and 2013 were included-other data back to 2008 were used to support the analyses. Rates of screening for GDM, rates of registration on the NGDR, and rates of follow-up laboratory screening for type 2 diabetes are reported. RESULTS: Estimated GDM screening rates were 86% in SA and 97% in VIC. Rates of registration on the NGDR ranged from 73% in SA (2013) to 91% in VIC (2013). During the study period rates of screening at six weeks postpartum ranged from 43% in SA (2012) to 58% in VIC (2013). There was little evidence of recall letters resulting in screening 12 months follow-up. CONCLUSIONS: GDM Screening and NGDR registration was effective in Australia. Recall by mail-out to young mothers and their GP's for type 2 diabetes follow-up testing proved ineffective.

Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study.

BACKGROUND: Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. METHODS: In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. FINDINGS: Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n=4895) or placebo (n=4900) in the FIELD study. Uric acid concentrations fell by 20·2% (95% CI 19·9-20·5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0·06 mmol/L or 1 mg/dL) and remained -20·1% (18·5-21·7, p<0·0001) lower in patients taking fenofibrate than in those on placebo in a random subset re-measured at 1 year. With placebo allocation, there were 151 (3%) first gout events over 5 years, compared with 81 (2%) among those allocated fenofibrate (HR with treatment 0·54, 95% CI 0·41-0·70; p<0·0001). In the placebo group, the cumulative proportion of patients with first gout events was 7·7% in patients with baseline uric acid concentration higher than 0·36 mmol/L and 13·9% in those with baseline uric acid concentration higher than 0·42 mmol/L, compared with 3·4% and 5·7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0·48, 95% CI 0·37-0·60; p<0·0001) compared with placebo. INTERPRETATION: Fenofibrate lowered uric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes. FUNDING: None.

Prevention of type 2 diabetes by lifestyle intervention in an Australian primary health care setting: Greater Green Triangle (GGT) Diabetes Prevention Project.

BACKGROUND: Randomised controlled trials demonstrate a 60% reduction in type 2 diabetes incidence through lifestyle modification programmes. The aim of this study is to determine whether such programmes are feasible in primary health care. METHODS: An intervention study including 237 individuals 40-75 years of age with moderate or high risk of developing type 2 diabetes. A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004-2006. Main outcome measures taken at baseline, three, and 12 months included weight, height, waist circumference, fasting plasma glucose and lipids, plasma glucose two hours after oral glucose challenge, blood pressure, measures of psychological distress and general health outcomes. To test differences between baseline and follow-up, paired t-tests and Wilcoxon rank sum tests were performed. RESULTS: At twelve months participants' mean weight reduced by 2.52 kg (95% confidence interval 1.85 to 3.19) and waist circumference by 4.17 cm (3.48 to 4.87). Mean fasting glucose reduced by 0.14 mmol/l (0.07 to 0.20), plasma glucose two hours after oral glucose challenge by 0.58 mmol/l (0.36 to 0.79), total cholesterol by 0.29 mmol/l (0.18 to 0.40), low density lipoprotein cholesterol by 0.25 mmol/l (0.16 to 0.34), triglycerides by 0.15 mmol/l (0.05 to 0.24) and diastolic blood pressure by 2.14 mmHg (0.94 to 3.33). Significant improvements were also found in most psychological measures. CONCLUSION: This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care settings, with reductions in risk factors approaching those observed in clinical trials.

Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with Type 2 diabetes mellitus.

Severe combined hyperlipidaemia has occasionally been associated with infiltration of tissues in addition to arteries and the skin. We report a woman with Type 2 diabetes mellitus (DM) and severe combined hyperlipidaemia who developed retinal lipid infiltration, resulting in blindness. A 61-year-old woman with a 15-year history of Type 2 DM was admitted following a two-week history of progressive visual loss. Examination identified lipid infiltration into the retina. Phenotypically she had severe combined hyperlipidaemia with elevated IDL cholesterol and a broad beta band on lipoprotein electrophoresis, raising the possibility of familial dysbetalipoproteinaemia. However, gene sequencing analysis indicated that the patient was homozygous for the E3/E3 allele of the ApoE gene with no mutations detected in either the coding region or intron-exon boundaries. Her lipid profile improved following dietary therapy and gemfibrozil treatment, but this had little effect on either her fundal appearances or her visual acuity. Type 2 DM plays a vital role both in allowing expression of severe combined hyperlipoproteinaemia, in addition to serving as a risk factor for complications such as tissue infiltration.

Epigenetic Markers to Predict Conversion From Gestational Diabetes to Type 2 Diabetes.

CONTEXT: Lifestyle factors mediate epigenetic changes that can cause chronic diseases. Although animal and laboratory studies link epigenetic changes to diabetes, epigenetic information in women with gestational diabetes (GDM) and type 2 diabetes is lacking. OBJECTIVE: This study sought to measure epigenetic markers across pregnancy and early postpartum and identify markers that could be used as predictors for conversion from GDM to type 2 diabetes. DESIGN: Global histone H3 dimethylation was measured in white blood cells at three time points: 30 wk gestation, 8-10 wk postpartum, and 20 wk postpartum, from four groups of women with and without diabetes. SETTING AND PARTICIPANTS: A total of 39 participants (six to nine in each group) were recruited including: nondiabetic women; women with GDM who developed postpartum type 2 diabetes; women with GDM without postpartum type 2 diabetes; and women with type 2 diabetes. MAIN OUTCOME MEASURE: Percentages of dimethylation of H3 histones relative to total H3 histone methylation were compared between diabetic/nondiabetic groups using appropriate comparative statistics. RESULTS: H3K27 dimethylation was 50-60% lower at 8-10 and 20 wk postpartum in women with GDM who developed type 2 diabetes, compared with nondiabetic women. H3K4 dimethylation was 75% lower at 8-10 wk postpartum in women with GDM who subsequently developed type 2 diabetes compared with women who had GDM who did not. CONCLUSIONS: The percentage of dimethylation of histones H3K27 and H3K4 varied with diabetic state and has the potential as a predictive tool to identify women who will convert from GDM to type 2 diabetes.

Coaching patients On Achieving Cardiovascular Health (COACH): a multicenter randomized trial in patients with coronary heart disease.

BACKGROUND: Disease management programs in which drugs are prescribed by dietitians or nurses have been shown to improve the coronary risk factor profile in patients with coronary heart disease. However, those disease management programs in which drugs are not prescribed by allied health professionals have not improved coronary risk factor status. The objective of the Coaching patients On Achieving Cardiovascular Health (COACH) study was to determine whether dietitians or nurses who did not prescribe medications could coach patients with coronary heart disease to work with their physicians to achieve the target levels for their total cholesterol (TC) and other risk factors. METHODS: Multicenter randomized controlled trial in which 792 patients from 6 university teaching hospitals underwent a stratified randomization by cardiac diagnosis within each hospital: 398 were assigned to usual care plus The COACH Program and 394 to usual care alone. Patients in The COACH Program group received regular personal coaching via telephone and mailings to achieve the target levels for their particular coronary risk factors. There was one coach per hospital. The primary outcome was the change in TC (DeltaTC) from baseline (in hospital) to 6 months after randomization. Secondary outcomes included measurement of a wide range of physical, nutritional, and psychological factors. The analysis was performed by intention to treat. RESULTS: The COACH Program achieved a significantly greater DeltaTC than usual care alone: the mean DeltaTC was 21 mg/dL (0.54 mmol/L) (95% confidence interval [CI], 16-25 mg/dL [0.42-0.65 mmol/L]) in The COACH Program vs 7 mg/dL (0.18 mmol/L) (95% CI, 3-11 mg/dL [0.07-0.29 mmol/L]) in the usual care group (P<.0001). Thus, the reduction in TC from baseline to 6 months after randomization was 14 mg/dL (0.36 mmol/L) (95% CI, 8-20 mg/dL [0.20-0.52 mmol/L]) greater in The COACH Program group than in the usual care group. Coaching produced substantial improvements in most of the other coronary risk factors and in patient quality of life. CONCLUSIONS: Coaching, delivered as The COACH Program, is a highly effective strategy in reducing TC and many other coronary risk factors in patients with coronary heart disease. Coaching has potential effectiveness in the whole area of chronic disease management.