Left ventricular mass in patients with type 2 diabetes is independently associated with central but not peripheral pulse pressure

An increase in left ventricular mass (LVM) occurs in the presence of type 2 diabetes, apparently independent of hypertension (1), but the determinants of this process are unknown. Brachial blood pressure is not representative of that at the ascending aorta (2) because the pressure wave is amplified from central to peripheral arteries. Central blood pressure is probably more clinically important since local pulsatile pressure determines adverse arterial and myocardial remodeling (3,4). Thus, an inaccurate assessment of the contribution of arterial blood pressure to LVM may occur if only brachial blood pressure is taken into consideration. In this study we sought the contribution of central blood pressure (and other interactive factors known to affect wave reflection, e.g., glycemic control and total arterial compliance) to LVM in patients with type 2 diabetes.

Determinants of exercise capacity in patients with type 2 diabetes

OBJECTIVE - Type 2 diabetes is associated with reduced exercise capacity, but the cause of this association is unclear. We sought the associations of impaired exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS - Subclinical left ventricular (LV) dysfunction was sought from myocardial strain rate and the basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2 diabetes (aged 56 +/- 10 years, 91 men), good quality echocardiographic images, and negative exercise echocardiograms. The same measurements were made in 56 control subjects (aged 53 +/- 10 years, 29 men). Exercise capacity was calculated in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart rate difference between peak and 1 min after exercise. In subjects with type 2 diabetes, exercise capacity was correlated with clinical, therapeutic, biochemical, and echocardiographic variables, and significant independent associations were sought using a multiple linear regression model. RESULTS - Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2 diabetes. Exercise capacity was associated with age (r- = -0.37, P < 0.001), male sex (r = 0.26, P = 0.001), BMI (r = -0.19, P = 0.012), HbA(1c) (AlC; r = -0.22, P = 0.009), Em (r = 0.43, P < 0.001), HRR (r = 0.42, P < 0.001), diabetes duration (r = -0.18, P = 0.021), and hypertension history (r = -0.28, P < 0.001). Age (P < 0.001), male sex (P = 0.007), BMI (P = 0.001), Em (P = 0.032), HRR (P = 0.013), and AlC (P = 0.0007) were independent predictors of exercise capacity. CONCLUSIONS - Reduced exercise capacity in patients with type 2 diabetes is associated with diabetes control, subclinical LV dysfunction, and impaired HRR.

The TAF5L gene on chromosome 1q42 is associated with type 1 diabetes in Russian affected patients

Type 1 diabetes (T1D) is a multifactorial autoimmune disease, with strong genetic component. Several susceptibility loci contribute to genetic predisposition to T1D. One of these loci have been mapped to chromosome 1q42 in UK and US joined affected family data sets but needs to be replicated in other populations. In this study, we evaluated sixteen microsatellites located on 1q42 for linkage with T1D in 97 Russian affected sibling pairs. A 2.7-cm region of suggestive linkage to T1D between markers D1S1644 and D1S225 was found by multipoint linkage analysis. The peak of linkage was shown for D1S2847 (P = 0.0005). Transmission disequilibrium test showed significant undertransmission of the 156-bp allele of D1S2847 from parents to diabetic children (28 transmissions vs. 68 nontransmissions, P = 0.043) in Russian affected families. A preferential transmission from parents to diabetic offspring was also shown for the T(-25) and T1362 alleles of the C/T(-25) and C/T1362 dimorphisms, both located at the TAF5L gene, which is situated 103 kb from D1S2847. Together with the A/C744 TAF5L SNP, these markers share common T(-25)/A744/T1362 and C(-25)/C744/T1362 haplotypes associated with higher and lower risk of diabetes (Odds Ratio = 2.15 and 0.62, respectively). Our results suggest that the TAF5L gene, encoding TAF5L-like RNA polymerase II p300/CBP associated factor (PCAF)-associated factor, could represent the susceptibility gene for T1D on chromosome 1q42 in Russian affected patients.

Olanzapine treatment is associated with reduced high molecular weight adiponectin in serum: A potential mechanism for Olanzapine-induced insulin resistance in patients with schizophrenia

Treatment of schizophrenia with olanzapine and other atypical antipsychotic agents is associated with insulin resistance and diabetes mellitus. The mechanism for this is not understood. Adiponectin is an insulin-sensitizing cytokine secreted by adipocytes. It is present in serum in multimers of varying size. Trimers and hexamers are referred to as low molecular weight (LMW) adiponectin. Larger multimers (12-, 18-, and 24-mers) have been designated high molecular weight (HMW) adiponectin and seem responsible for the insulin-sensitizing action of this adipokine. The aim of this study was to examine total adiponectin and LMW and HMW multimers in serum from patients with schizophrenia treated with either olanzapine (n = 9) or other typical antipsychotics (n = 9) and compare results with 16 healthy sex-, body mass index-, and age-matched controls. The effects of olanzapine on adiponectin protein expression and secretion in in vitro-differentiated primary human adipocytes were also examined. Patients receiving olanzapine had significantly lower total serum adiponectin as compared with those on conventional treatment and controls (5.23 +/- 1.53 ng/mL vs. 8.20 +/- 3.77 ng/mL and 8.78 +/- 3.8 ng/mL; P < 0.05 and P < 0.01, respectively). The HMW adiponectin was also reduced in patients on olanzapine as compared with the disease and healthy control groups (1.67 +/- 0.96 ng/mL vs. 3.87 +/- 2.69 ng/mL and 4.07 +/- 3.2 ng/mL; P < 0.05 for both). The LMW adiponectin was not different between patient groups (P = 0.15) but lower in patients on olanzapine as compared with controls (3.56 +/- 10.85 ng/mL vs. 4.70 +/- 1.4 ng/mL; P < 0.05). In vitro, short duration (up to 7 days) olanzapine exposure had no effect on total adiponectin expression or multimer composition of secreted protein. In summary, this study demonstrates a correlation between olanzapine treatment and reduced serum adiponectin, particularly HMW multimers. This may not be a direct effect of olanzapine on adipocyte expression or secretion of adiponectin. These observations provide insights into possible mechanisms for the association between olanzapine treatment and insulin resistance.

Diagnosis of diabetes mellitus: case of different cutoff values: A data mining approach

Objective: An estimation of cut-off points for the diagnosis of diabetes mellitus (DM) based on individual risk factors. Methods: A subset of the 1991 Oman National Diabetes Survey is used, including all patients with a 2h post glucose load >= 200 mg/dl (278 subjects) and a control group of 286 subjects. All subjects previously diagnosed as diabetic and all subjects with missing data values were excluded. The data set was analyzed by use of the SPSS Clementine data mining system. Decision Tree Learners (C5 and CART) and a method for mining association rules (the GRI algorithm) are used. The fasting plasma glucose (FPG), age, sex, family history of diabetes and body mass index (BMI) are input risk factors (independent variables), while diabetes onset (the 2h post glucose load >= 200 mg/dl) is the output (dependent variable). All three techniques used were tested by use of crossvalidation (89.8%). Results: Rules produced for diabetes diagnosis are: A- GRI algorithm (1) FPG>=108.9 mg/dl, (2) FPG>=107.1 and age>39.5 years. B- CART decision trees: FPG >=110.7 mg/dl. C- The C5 decision tree learner: (1) FPG>=95.5 and 54, (2) FPG>=106 and 25.2 kg/m2. (3) FPG>=106 and =133 mg/dl. The three techniques produced rules which cover a significant number of cases (82%), with confidence between 74 and 100%. Conclusion: Our approach supports the suggestion that the present cut-off value of fasting plasma glucose (126 mg/dl) for the diagnosis of diabetes mellitus needs revision, and the individual risk factors such as age and BMI should be considered in defining the new cut-off value.

DINÂMICA PSÍQUICA E EFICÁCIA ADAPTATIVA DE PACIENTES COM DIABETES MELLITUS TIPO 2

O diabetes é uma doença crônica conhecida há aproximadamente 3.500 anos e que atinge, atualmente, cerca de 18,8 milhões de pessoas no mundo, sendo, portanto, de grande interesse a diversos pesquisadores das mais variadas áreas. Esta doença é resultante de uma insuficiência de insulina, que desempenha papel fundamental nos processos metabólicos do organismo. A incidência do Diabetes Mellitus tipo 2 tem apresentado um considerável crescimento nas últimas décadas, principalmente decorrente da elevada expectativa de vida e, também, pelo resultado de comportamentos destrutivos a saúde, como o abuso de substâncias, dieta inadequada e um estilo de vida sedentário. O presente estudo teve por objetivos avaliar a Qualidade de Vida, a dinâmica psíquica, a eficácia adaptativa e verificar os níveis glicêmicos de pessoas com Diabetes Mellitus tipo 2 participantes de um grupo psicoeducativo. Participaram deste estudo 14 pessoas com Diabetes Mellitus tipo 2. Os instrumentos utilizados foram: 1. Escala da Associação Brasileira de Institutos de Pesquisa de Mercado (ABIPEME); 2. Escala Diagnóstica Adaptativa Operacionalizada (EDAO); 3. Teste das Relações Objetais de Phillipson (TRO); e, 4. WHOQOL-bref. Os resultados mostraram que alguns pacientes apresentaram uma melhora significativa em seus níveis glicêmicos após a realização do grupo psicoeducativo, mesmo verificando que alguns não atingiram ainda bom controle de sua glicemia. A qualidade de vida destes participantes apresentou-se com níveis muito bons. Ao avaliar a eficácia adaptativa e a dinâmica psíquica destes participantes, verificou-se o quanto é difícil aceitar que se tem uma doença crônica e ter atitudes para realizar o tratamento adequado. Concluímos que para estas pessoas com diabetes poderem aderir ao tratamento é necessário que ele apresente uma boa capacidade de solucionar conflitos, e, apresente seu mundo interno ligado à posição depressiva. Se estes fatores estiverem equilibrados o estilo de vida e o bem-estar desses pacientes serão positivos, de modo que eles possam apresentar consequentemente um bom prognóstico com menos complicações da doença durante mais tempo de vida.

QUALIDADE DE VIDA, SUPORTE SOCIAL E CONTROLE GLICÊMICO EM PORTADORES DE DIABETES MELLITUS TIPO2

Diabetes Mellitus é uma doença crônica degenerativa que impõe uma série de limitações em função da necessidade de tratamento constante. Por isso, considerou-se que o estudo da qualidade de vida e suporte social poderia trazer conhecimento para melhorar a qualidade das intervenções para estes pacientes. O objetivo deste trabalho foi avaliar a qualidade de vida, suporte social e controle glicêmico de portadores de Diabetes Mellitus tipo2. Trata-se de um estudo descritivo e transversal, desenvolvido com 120 pacientes de ambos os gêneros, atendidos no ambulatório de endocrinologia de um hospital situado na cidade de São Bernardo do Campo. Para coleta dos dados foram utilizados os seguintes instrumentos: questionário para caracterização da população, questionário de qualidade de vida (WHOQOL-BREF) e a Escala de Percepção de Suporte Social (EPSS). Os dados referentes ao controle glicêmico foram coletados nos prontuários dos pacientes. Para análise dos dados utilizou-se à estatística descritiva e provas estatísticas (Pearson, QuiQuadrado, Exato de Fisher, Anova e Pos-hoc). Os resultados indicaram que o domínio das relações sociais foi o que mais contribuiu a qualidade de vida. E as variáveis tempo de diagnóstico, insulinoterapia, número de dependentes, escolaridade, dieta e medicação interferiram na qualidade de vida e na qualidade do tratamento. Estes resultados chamam a atenção para que as avaliações médicas devam ser atreladas a avaliações da qualidade de vida, suporte social e também variáveis que interferem na qualidade do tratamento para que, desta forma possam redimensionar ou melhorar fazeres ligados às intervenções com estes pacientes.

Ocular and systemic markers for vascular function in those at risk of type 2 diabetes mellitus and cardiovascular disease

The devastating impact of Type 2 Diabetes Mellitus (T2DM) -related morbidity and mortality on global healthcare is escalating with higher prevalences of obesity, poor diet, and sedentary lifestyles. Therefore, the clinical need for early diagnosis and prevention in groups of high-risk individuals is necessary. The purpose of this thesis was to investigate the use of surrogate markers, namely retinal vascular function, to determine future vascular endothelial dysfunction, atherosclerosis, large vessel disease and cardiovascular risk in certain groups. This namely covered normoglycaemic and normotensive South Asians (SAs), those with Impaired-Glucose Tolerance (IGT) and individuals with a familial history (FH) of T2DM. Additionally the effect of overweight and obesity was studied. The techniques and modified protocols adopted for this thesis involved the investigation of endothelial function by means of vascular reactivity at the ocular and systemic level. Furthermore, the relationships between retinal and systemic function with circulating markers for endothelial cell function and cardiovascular risk markers were explored. The principal studies and findings of the research were: Vascular Function in Normoglycaemic Individuals with and without a FH of T2DM WE FH individuals exhibited higher levels of total cholesterol levels that correlated well with the retinal arterial dilation amplitude to flicker light stimulus. However this did not extend to noticeable differences in markers for endothelial cell damage and impaired retinal and systemic function. Vascular Function in Normoglycaemic South-Asians vs. White-Europeans without a FH and Vascular Disturbances Compared to healthy WEs (normo -glycaemic and -tensive), SA participants exhibited levels of dyslipidaemia and a state of oxidative stress that extended to impaired vascular function as detected by reduced brachial artery flow-mediated dilation, slower retinal arterial vessel dilation reaction times (Appendix 3) and steeper constriction profiles. Furthermore, gender sub-group analysis presented in a sub-chapter shows that SA males demonstrated 24-hour systemic blood pressure (BP) and heart rate variability (HRV) abnormalities and heightened cardiovascular disease (CVD) risk. Vascular Function in Individuals Newly Diagnosed with IGT as compared to Normoglycaemic Healthy Controls Newly-diagnosed WE and SA IGT patients showed a greater risk for CVD and T2DM progression by means of 24-hour BP abnormalities, dyslipidaemia, increased carotid artery intimal-media thickness (c-IMT), Framingham scores and cholesterol ratios. Additionally, pre-clinical markers for oxidative stress and endothelial dysfunction, as evident by significantly lower levels of plasma glutathione and increased levels of von-Willebrand factor in IGT individuals, extended to impaired vascular systemic and retinal function compared to normal controls. This originally shows retinal, systemic and biochemical disturbances in newly-diagnosed IGT not previously reported before. Vascular Function in Normal, Overweight and Obese Individuals of SA and WE Ethnicity In addition to the intended study chapters, the thesis also investigated the influence of obesity and overweight on vascular function. Most importantly, it was found for the first time that compared to lean individuals it was overweight and not obese individuals that exhibited signs of vascular systemic and ocular dysfunction that was evident alongside markers of atherosclerosis, CVD risk and endothelial damage.

Somatic cell gene therapy for diabetes mellitus: engineering a surrogate B-cell

Improved methods of insulin delivery are required for the treatment of insulin-dependent diabetes mellitus (IDDM) to achieve a more physiological profile of glucose homeostasis. Somatic cell gene therapy offers the prospect that insulin could be delivered by an autologous cell implant, engineered to secrete insulin in response to glucose. This study explores the feasibility of manipulating somatic cells to behave as a surrogate insulin-secreting β-cells. Initial studies were conducted using mouse pituitary AtT20 cells as a model, since these cells possess an endogenous complement of enzymes capable of processing proinsulin to mature insulin. Glucose sensitive insulin secretion was conferred to these cells by transfection with plasmids containing the human preproinsulin gene (hppI-1) and the GLUT2 gene for the glucose transporter isoform 2. Insulin secretion was responsive to changes in the glucose concentration up to about 50μM. Further studies to up-rate this glucose sensitivity into the mM range will require manipulation of the hexokinase and glucokinase enzymes. Intraperitoneal implantation of the manipulated AtT20 cells into athymic nude mice with streptozotocin-induced diabetes resulted in decreased plasma glucose concentrations. The cells formed vascularised tumours in vivo which were shown to contain insulin-secreting cells. To achieve proinsulin processing in non-endocrine cells, co-transfection with a suitable enzyme, or mutagenesis of the proinsulin itself are necessary. The mutation of the human preproinsulin gene to the consensus sequence for cleavage by the subtilisin-like serine protease, furin, was carried out. Co-transfection of human fibroblasts with wild-type proinsulin and furin resulted in 58% conversion to mature insulin by these cells. Intraperitoneal implantation of the mature-insulin secreting human fibroblasts into the diabetic nude mouse animal model gave less encouraging results than the AtT20 cells, apparently due to poor vascularisation. Cell aggregations removed from the mice at autopsy were shown to contain insulin secreting cells only at the periphery. This thesis provides evidence that it is possible to construct, by cellular engineering, a glucose-sensitive insulin-secreting surrogate β-cell. Therefore, somatic cell gene therapy offers a feasible alternative for insulin delivery in IDDM patients.

Severe visual impairment due to diabetes mellitus:can this be influenced by community & hospital retinal screening and formal hospital diabetic annual review?

Purpose: Diabetes is a leading cause of visual impairment in working age population in the UK. This study looked at the causes of Severe Visual Impairment(SVI) in the patients attending diabetic eye clinic and influence on the rate of SVI, over a 12 year period, after introducing retinal screening programmes in the hospital and the community in 1993 (review in 1992, 1998 & 2004). Methods: Medical records of all the patients attending the diabetic eye clinic over a period of 5months(April to August) in 1992, 1998 and 2004 were reviewed. The data collected for each patient included age, sex, ethnic origin, diabetes (type,duration &treatment), the best corrected visual acuity (present and at time of presentation), type and duration of retinopathy and attendance record to both diabetic clinic and diabetic eye clinic. In this study, SVI is defined as a visual acuity of 6/36 or worse in at least one eye. Results: In 1992, of a total 245 patients, 58patients(23.6%) had SVI {38 (15.5% of total) due to diabetic retinopathy [31(12.6%) maculopathy, 2(0.8%) vitreous haemorrhage and 5(2%) retinal detachment] and 20(8.1%) due to non–diabetic retinopathy causes}. In 1998, of a total 297, 77patients(25.9%) had SVI {33(11.1% of total) due to diabetic retinopathy [19(6.4%) maculopathy, 9(3%) proliferative retinopathy, 8(2.7%) vitreous haemorrhage and 3(1%) retinal detachment]and 44(14.8%)due to non–diabetic retinopathy}. In 2004, of a total 471, 72patients(15.2%) had SVI{46(9.7%of total) due to diabetic retinopathy [37(7.8%) maculopathy, 1(0.2%) proliferative retinopathy, 6(1.8%) vitreous haemorrhage and 2(0.4%) retinal detachment]and 26(5.5%) due to non– diabetic retinopathy causes}. Conclusions: Introduction of formalised annual diabetic review including retinal screening and a community retinal screening programme has reduced the rate of severe visual impairment due to diabetic retinopathy, in patients attending diabetic eye clinic, from 15.5% in1992 to 9.7% in2004. Keywords: diabetic retinopathy

New drugs for type 2 diabetes mellitus:what is their place in therapy?

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulforylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women. Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagonlike peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on P cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety. In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.

Lack of effect of aspirin in primary CV prevention in type 2 diabetic patients with nephropathy:results from 8 years follow-up of NID-2 study

The risk-to-benefit ratio for the use of low dose of aspirin in primary cardiovascular (CV) prevention in patients with diabetes mellitus remains to be clarified. We assessed the effect of aspirin on risk of CV events in type 2 diabetic patients with nephropathy, in order to verify the usefulness of Guidelines in clinical practice. We carried out a prospective multicentric study in 564 patients with type 2 diabetic nephropathy free of CV disease attending outpatient diabetes clinics. A total of 242 patients received antiplatelet treatment with aspirin 100 mg/day (group A), and 322 were not treated with antiplatelet drugs (group B). Primary end point was the occurrence of total major adverse cardio-vascular events (MACE). Secondary end points were the relative occurrence of fatal MACE. The average follow-up was 8 years. Total MACE occurred in 49 patients from group A and in 52 patients from group B. Fatal MACE occurred in 22 patients from group A and in 20 from group B; nonfatal MACE occurred in 27 patients from group A and in 32 patients from group B. Kaplan-Meier analysis did not show a statistically significant difference of cumulative MACE between the two groups. A not statistically significant difference in the incidence of both fatal (p = 0.225) and nonfatal CV events (p = 0.573) between the two groups was observed. These results were confirmed after adjustment for confounders (HR for MACE 1.11, 95 % CI 0.91-1.35). These findings suggest that low dose of aspirin is ineffective in primary prevention for patients with nephropathy. © 2014 Springer-Verlag Italia.

Metformin in patients with type 2 diabetes and kidney disease:a systematic review

IMPORTANCE: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining tometformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014.We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety ofmetformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus-use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2

Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p<0.0005) and between groups (p<0.0005). However, the refractive error components and ocular aberrations were not found to alter significantly over the day in either the diabetic patients or the control subjects (p>0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients. © 2012 Huntjens et al.

Obstructive sleep apnoea is associated with sight threatening retinopathy and predicts the developement of preproliferative and proliferative retinopathy in patients with type 2 diabetes:a longitudinal analysis

troduct I on . An observational longitudinal study. P ur P ose . Assess the relationship between obstructive sleep apnoea (OSA) and DR cross-sectionally and longitudinally. M ethods . Adults with Type 2 diabetes mellitus (T2DM), who were re - cruited from a hospital-based diabetes clinic in the UK. Patients with pre-existing OSA, end-stage renal disease and non-diabetic retinopa - thy were excluded. OSA (apnoea hypopnea index ≥ 5 events/hour) was assessed by a single overnight home-based cardio-respiratory study (Alice PDX, Philips Respironics, USA). DR was assessed us - ing retinal images between 2007 and 2012. Sight threatening diabetic retinopathy (STDR) was defined as presence of pre-proliferative or proliferative DR, maculopathy or photocoagulation. Advanced DR was defined as pre-proliferative or proliferative DR. r esults . 199 patients were included (57.3% (n=114) men, 47.7% (n=95) White Europeans). STDR and OSA prevalence were 38.7% (n=77) and 62.8% respectively. A t b A sel I ne . STR prevalence was higher in patients with OSA (OSA+) compared to those without OSA (OSA-) [48.8% n=61 vs. 21.6% n=16, p<0.001]. After adjustment for confounders, OSA remained independently associated with STR (OR 3.7, 95% CI 1.6-8.9, p=0.006), maculopathy (OR 4.5, 95% CI 1.8-11.4, p=0.002) and advanced DR (OR 3.9, 95% CI 1.02-15.3, p=0.047). Mild and moderate to severe OSA were independently associated with STR and maculopathy and only moderate to severe OSA was associated with advanced DR following adjustment for con - founders. l ong I tud I n A lly . Over the follow-up period of (4.4±1 years), more OSA+ patients progressed from no or background DR to advanced DR (15.3% (n=17) vs. 3% (n=2), p=0.01). OSA was an independent pre - dictor of advanced DR development after adjustment for confounders (OR 6.6, 95% CI 1.2-35.1, p=0.03). OSA did not predict the develop - ment of maculopathy. c onclus I ons . OSA is independently associated with STR and predicts the development of preproliferative and proliferative DR. Intervention - al studies are needed to assess the impact of OSA treatment on DR.