Urinary C-peptide Creatinine Ratio in pregnant women with normal glucose tolerance and type 1 diabetes: evidence for insulin secretion

Hypothesis In pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes. Research design and methods UCPCR and serum C peptide were measured in 90 glucose-tolerant women at 0 and 120 min during a 75 g oral glucose tolerance test (OGTT) at 28 weeks of gestation. UCPCR was measured in 2 samples obtained over 10 weeks apart in 7 pregnant women with longstanding type 1 diabetes. Results UCPCROGTT and serum C peptideOGTT of glucose-tolerant women were significantly correlated at 0 and 120 min (rs0.675, 0.541 respectively, p<0.0001). All 7 pregnant women with type 1 diabetes had detectable first sample UCPCR (median (range) 49 (6–1038) pmol/mmol) that rose in 6 women by 477 (29–1491) pmol/mmol. Conclusions Detectable UCPCR in pregnant women with normal glucose tolerance and type 1 diabetes is likely to reflect endogenous insulin secretion and hence β-cell activity

Insulin-associated weight gain in obese type 2 diabetes mellitus patients: What can be done?

Insulin therapy (IT ) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT , which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin‐associated weight gain (IAWG ) is reported to occur in the first year of initiating IT , predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch‐up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co‐morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT , that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG , and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain

Ethnic inequalities in the treatment and outcome of diabetes in three English Primary Care Trusts

BACKGROUND:Although the prevalence of diabetes is three to five times higher in UK South Asians than Whites, there are no reports of the extent of ethnicity recording in routine general practice, and few population-based published studies of the association between ethnicity and quality of diabetes care and outcomes. We aimed to determine the association between ethnicity and healthcare factors in an English population.METHODS:Data was obtained in 2002 on all 21,343 diabetic patients registered in 99% of all computerised general practitioner (GP) practices in three NW London Primary Care Trusts (PCTs), covering a total registered population of 720,000. Previously practices had been provided with training, data entry support and feedback. Treatment and outcome measures included drug treatment and blood pressure (BP), total cholesterol and haemoglobin A1c (HbA1c) levels.RESULTS:Seventy per cent of diabetic patients had a valid ethnicity code. In the relatively older White population, we expected a smaller proportion with a normal BP, but BP differences between the groups were small and suggested poorer control in non-White ethnic groups. There were also significant differences between ethnic groups in the proportions of insulin-treated patients, with a smaller proportion of South Asians - 4.7% compared to 7.1% of Whites - receiving insulin, although the proportion with a satisfactory HbA1c was smaller- 25.6% compared to 37.9%.CONCLUSION:Recording the ethnicity of existing primary care patients is feasible, beginning with patients with established diseases such as diabetes. We have shown that the lower proportion of South Asian patients with good diabetes control, and who are receiving insulin, is at least partly due to poorer standards of care in South Asians, although biological and cultural factors could also contribute. This study highlights the need to capture ethnicity data in clinical trials and in routine care, to specifically investigate the reasons for these ethnic differences, and to consider more intensive management of diabetes and education about the disease in South Asian patient

A randomized controlled trial: the effect of inulin on weight management and ectopic fat in subjects with prediabetes.

BACKGROUND: Fat infiltration of the liver, muscle and pancreas is associated with insulin resistance and risk of diabetes. Weight loss reduces ectopic fat deposition and risk of diabetes, but is difficult to sustain to due to compensatory increases in appetite. Fermentable carbohydrates have been shown to decrease appetite and food intake, and promote weight loss in overweight subjects. In animal studies, fermentable carbohydrate reduces ectopic fat independent of weight loss. We aimed to investigate the effect of the fermentable carbohydrate inulin on weight maintenance, appetite and ectopic fat in subjects with prediabetes. METHODS: Forty-four subjects with prediabetes were randomized to 18 weeks' inulin or cellulose supplementation. During weeks 1-9 (weight loss phase) all subjects had four visits with a dietitian to guide them towards a 5 % weight loss. During weeks 10-18 (weight maintenance phase) subjects continued taking their assigned supplementation and were asked to maintain the weight they had lost but were offered no further support. All subjects attended study sessions at baseline, 9 and 18 weeks for measurement of weight; assessment of adipose tissue and ectopic fat content by magnetic resonance imaging and magnetic resonance spectroscopy; glucose, insulin and GLP-1 levels following a meal tolerance test; and appetite by ad libitum meal test and visual analogue scales. RESULTS: Both groups lost approximately 5 % of their body weight by week nine (-5.3 ± 0.1 % vs -4.3 ± 0.4 %, p = 0.13, but the inulin group lost significantly more weight between 9 and 18 weeks (-2.3 ± 0.5 % vs -0.6 ± 0.4 %, p = 0.012). Subjects taking inulin had lower hepatic (p = 0.02) and soleus muscle (p < 0.05) fat content at 18 weeks compared to control even after controlling for weight loss and consumed less at the ad libitum meal test (p = 0.027). Fasting glucose significantly decreased at week nine only (p = 0.005), insulin concentrations did not change, and there was a significant increase in GLP-1 in the cellulose group at 9 and 18 weeks (p < 0.03, p < 0.00001). CONCLUSION: Inulin may have a two-pronged effect on the risk of diabetes by 1) promoting weight loss 2) reducing intrahepatocellular and intramyocellular lipid in people with prediabetes independent of weight loss

Low-energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin: a randomized trial

OBJECTIVES: The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT. RESEARCH DESIGN AND METHODS: In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL). RESULTS: Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01). CONCLUSIONS: Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success. TRIAL REGISTRATION NUMBER: ISRCTN21335883

Fine-structure diagnostics of neutral carbon toward HE 0515-4414

New high-resolution high signal-to-noise spectra of the $z=1.15$ damped Lyman $\alpha$ (DLA) system toward the quasi-stellar object HE 0515-4414 reveal absorption lines of the multiplets 2 and 3 in \ion{C}{i}. The resonance lines are seen in two components with total column densities of $\log N=13.79\pm0.01$ and $\log N=13.36\pm0.01$, respectively. The comparision of theoretical calculations of the relative fine-structure population with the ratios of the observed column densities suggests that the \ion{C}{i} absorbing medium is either very dense or exposed to very intense UV radiation. The upper limit on the local UV energy density is 100 times the galactic UV energy density, while the upper limit on the \ion{H}{i} number density is 110 cm$^{-3}$. The excitation temperatures of the ground state fine-structure levels of $T=15.7$ and $T=11.1$ K, respectively, are consistent with the temperature-redshift relation predicted by the standard Friedmann cosmology. The cosmic microwave background radiation (CMBR) is only a minor source of the observed fine-structure excitation.Comment: 5 pages, 5 figures, uses A&A macro package, gzipped tar archive, accepted by A&

Plasma free fatty acids do not provide the link between obesity and insulin resistance or β-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study

Aims To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and β-cell function. Methods An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. Results After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: β = −0.357; waist circumference: β = −0.380; body fat mass: β = −0.375) and disposition index (BMI: β = −0.215; waist circumference: β = −0.248; body fat mass: β = −0.221) and positively associated with acute insulin response to glucose [BMI: β = 0.200; waist circumference: β = 0.195; body fat mass β = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (β = −0.133), acute insulin response to glucose (β = −0.148) and disposition index [β = −0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. Conclusions Plasma free fatty acid levels have a modest negative association with insulin sensitivity, β-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or β-cell dysfunction

A comparison of validated methods used to assess impaired awareness of hypoglycaemia in type 1 diabetes: an observational study

Introduction Clarke, Gold and Pedersen are validated methods to assess awareness of hypoglycaemia. Identifying impaired awareness of hypoglycaemia (IAH) is critical for supporting people with structured education and diabetes technologies, to reduce harm of hypoglycaemia. This study compares the Clarke score, Gold score and Pedersen methods and their correlations with features of hypoglycaemia unawareness and patient characteristics, to evaluate the accuracy of the methods in identifying IAH. Methods This retrospective, observational questionnaire-based study collected routine clinical data from 100 people with type 1 diabetes. The questionnaire included the three validated scoring methods, frequency of severe and nocturnal hypoglycaemia, knowledge and worry of hypoglycaemia and hypoglycaemia symptom scores using the Edinburgh Hypoglycaemia Scale. Data were analysed for IAH prevalence and the associations with features of IAH. The concordance of Clarke, Gold and Pedersen methods was evaluated using Spearman’s correlation coefficient. Results The prevalence of IAH in this cohort identified by Clarke, Gold and Pedersen methods was 18%, 19% and 61% respectively. The mean autonomic symptom score in people with IAH was significantly reduced using the Clarke method (P = 0.0002) but not on Gold (P = 0.12) and Pedersen methods (P = 0.79). For people with IAH assessed using the Clarke method, scores for night-time worry regarding hypoglycaemia (P = 0.04) and self-reported frequency of nocturnal hypoglycaemia (P = 0.001) were increased. Spearman’s correlation coefficients between Pedersen and Clarke and Pedersen and Gold were Rs = 0.555 (P < 0.001) and Rs = 0.645 (P < 0.001) respectively. A moderate association was observed between Clarke and Gold Rs = 0.5669 (P < 0.001). Conclusion Whilst Clarke and Gold methods determined a similar prevalence of IAH, people identified with IAH assessed by the Clarke method had a significant association with the features and characteristics of IAH, including reduced autonomic symptoms. This study suggests that performing more than one score is important for a reliable risk assessment of IAH

Evolution of subclinical myocardial dysfunction detected by two-dimensional and three-dimensional speckle tracking in asymptomatic type 1 diabetic patients: a long-term follow-up study

Background We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up. Design and methods Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation. Results At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (−18.9 ± 2 vs −20.5 ± 2; P = 0.0002) and 3D-GLS (−17.5 ± 2 vs −19 ± 2; P = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: −18.4 ± 1 vs −19.2 ± 1; P = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease – long-term diabetes (GCS: −26 ± 3 vs −23.3 ± 3; P = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P = 0.04). Conclusions Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported