Risk of minor and major fetal malformations in diabetics with high haemoglobin A1c values in early pregnancy.

Maternal haemoglobin A1c (HbA1c) values were measured before the end of the 15th week of gestation in 142 pregnancies in women with insulin dependent diabetes. In pregnancies complicated by fetal malformations (n = 17) the mean initial HbA1c value was 9.5 (SD 1.8)% of the total haemoglobin concentration, which was significantly (p less than 0.001) higher than in pregnancies without malformations (8.0 (SD 1.4)%; n = 125). HbA1c values did not differ between pregnancies complicated by minor and major fetal malformations, but the rate of malformations showed a positive relation to the HbA1c value in early pregnancy (chi 2 = 11.9; p = 0.001). Fetal malformations occurred in six out of 17 pregnancies (35.3%) in mothers whose initial HbA1c value was 10% or more, in eight out of 62 pregnancies (12.9%) in mothers with initial values between 8.0% and 9.9%, and in only three out of 63 pregnancies (4.8%) in mothers with an initial value below 8.0%. These data support the hypothesis that the increased incidence of fetal malformations in mothers with insulin dependent diabetes is associated with maternal hyperglycaemia during organogenesis. Hence diabetic women who are planning to have a child--especially those with a high HbA1c value--should receive intensified metabolic control.     

Diabetes in prison: can good diabetic care be achieved?

OBJECTIVE--To investigate the clinical characteristics and metabolic control of diabetic patients given structured diabetic care in prison. DESIGN--Survey of diabetic men serving prison sentences during a 22 month period in a large British prison. SETTING--HM Prison, Walton, Liverpool. SUBJECTS--42 male diabetic prisoners, of whom 23 had insulin dependent and 19 non-insulin dependent diabetes. MAIN OUTCOME MEASURES--Episodes of diabetic instability, glycated haemoglobin concentrations, body mass index. RESULTS--No serious diabetic instability occurred. Between the initial assessment by the visiting consultant diabetologist and a second assessment 10 weeks later glycated haemoglobin concentrations had fallen from 10.8 (SD 2.9)% to 9.8 (2.4)% (p less than 0.05) in prisoners with insulin dependent diabetes and from 8.7 (1.9)% to 7.6 (1.2)% (p less than 0.05) in those with non-insulin dependent diabetes. Good glycaemic control continued, a mean glycated haemoglobin concentration of 7.6 (1.5)% being recorded in seven men remaining in prison for six to 18 months. Mean body mass index (weight (kg)/(height(m))2) did not change during the study (insulin dependent prisoners 23.3 (SD 2.1), non-insulin dependent prisoners 27.9 (3.8)). CONCLUSIONS--Good diabetic metabolic control is usual in prison, probably due to the rigid dietary regimen, no alcohol, and compliance with treatment. Many younger men had defaulted from their home diabetic clinics, and imprisonment allowed screening for diabetic complications and reassessment of treatment. Structured diabetic care should be offered in all prisons.     

Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure

The purpose of the study was to find out differences between treatments of diabetes type 2 after secondary oral antidiabetic drug failure. Three different methods of treatment were compared: lispro insulin in combination with metformin, glimepiride and metformin combination or two daily doses of biphasic insulin 30/70 together with bed-time NPH insulin. The study included 87 patients with diabetes mellitus type 2 randomly distributed into 3 different treatment groups. Fasting and postprandial glucose were analyzed by enzymatic colorimetric method and HbA1c was measured by ion exchange chromatography. HbA1c significantly decreased in all three study groups. The decrease was mostly expressed among patients treated with lispro and metformin. When focused on postprandial glucose control, antihyperglycemic metformin and insulin lispro therapy has greater impact on the overall metabolic control (decrease in level of HbA1c) in comparison with the above mentioned more traditional approaches.     

安立泽联合胰岛素治疗单独胰岛素降糖欠佳的高龄 2 型糖尿病患者临床观察

目的：观察安立泽应用于单独胰岛素治疗血糖控制欠佳的高龄2 型糖尿病患者的疗效及安全性。方法：200 例高龄2型糖尿 病胰岛素降糖欠佳的患者（空腹血糖控制在7.8-13.9mmol/L范围内）,随机分成对照组和治疗组,对照组采用胰岛素加安慰剂治 疗80 例;治疗组120 例,分为A、B、C三组,每组40 例,A、B、C三组分别在继续应用胰岛素治疗的基础上加服安立泽4mg/d、 5mg/d、6mg/d,疗程三个月。观测治疗组和对照组治疗前后FPG 及PPG、HbA1C、BMI 和胰岛素用量的改变及治疗的安全性。结 果：对照组和治疗组治疗前的各指标无明显差异（P＞0.05）;A、B、C三组在治疗后1 个月和3 个月FPG、PPG、HbA1C均有明显的 下降（P＜0.05,P＜0.01）,而对照组治疗前后FIG、PPG、HbA1C 略有下降,差异不明显（P＞0.05）;A、B、C 三组胰岛素的用量及体 重指数较治疗前均略有下降,三组间无显著性差异;对照组和治疗组的不良反应发生率无显著差异。结论：对高龄2 型糖尿病单 用胰岛素治疗血糖控制欠佳的患者,加用安立泽治疗,可使糖尿病相关指标得以良好的控制,减少糖尿病患者每日胰岛素用量, 临床毒副作用较小。     

Intensified conventional insulin treatment and neuropsychological impairment.

OBJECTIVE--To assess whether intensified insulin treatment, with an increased frequency of hypoglycaemic episodes, leads to cognitive deterioration. DESIGN--Prospective randomised trial of intensified conventional treatment and standard treatment. SETTING--Outpatient clinic for patients with insulin dependent diabetes. SUBJECTS--96 patients with insulin dependent diabetes, high blood glucose concentrations, and non-proliferative retinopathy were randomised to intensified conventional treatment (n = 44) or standard treatment (n = 52). MAIN OUTCOME MEASURES--Glycated haemoglobin concentration (metabolic control); the number of hypoglycaemic episodes reported by patients at each visit; results of computerised neuropsychological tests performed at entry and after five years. RESULTS--Mean glycated haemoglobin concentration during the study was 7.2% (SE 0.1%) with intensified conventional treatment and 8.7 (0.1%) with standard treatment (p less than 0.001). During five years 34 (77%, 95% confidence interval 53% to 100%) of the patients given intensified treatment and 29 (56%, 36% to 75%) of the others had at least one episode of serious hypoglycaemia (p less than 0.05). The intensified conventional treatment group had a mean of 1.1 episodes of serious hypoglycaemia per patient per year compared with 0.4 episodes in the standard treatment group. Results of the neuropsychological tests were similar in the two groups after five years. CONCLUSIONS--Intensified conventional insulin treatment led to lower blood glucose concentrations and a higher frequency of hypoglycaemic episodes, but patients showed no signs of cognitive deterioration.     

Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study.

OBJECTIVE--To study insulin dependent diabetic patients for change in non-proliferative retinopathy and its relation to glycaemic control and to various clinical background data. DESIGN--Prospective study with follow up for seven years. SETTING--Outpatient departments of university hospitals. MAIN OUTCOME MEASURES--Glycated haemoglobin concentration; degree of retinopathy. RESULTS--Retinopathy worsened by an overall increase in counts of microaneurysms and haemorrhages from 17 (SD 25) to 45 (58) (p = 0.005). Intensified insulin treatment and home blood glucose monitoring improved concentrations of glycated haemoglobin (HbA1) from 11.2% (2.2%) at the start of the study to a mean of 9.5% (1.5%) over the seven years of the study (p less than 0.0001). A mean value for HbA1 greater than 10% was associated with an increased risk of progression of retinopathy and a mean value less than 8.7% was associated with a diminished risk. Multiple regression analysis identified four independent variables as indicative of outcome of retinopathy after seven years: HbA1 value at baseline; the change in HbA1 from start to the mean level through the seven years; duration of diabetes; and retinopathy at start. Age, blood pressure, and urinary albumin excretion were not related to the presence or progression of retinopathy. CONCLUSION--Secondary intervention by long term lowering of glycated haemoglobin has a beneficial impact on non-proliferative retinopathy. A four factor regression model can determine patients at high risk of severe retinopathy.     

Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study.

Pioglitazone is a novel oral anti-diabetic agent belonging to the thiazolidinedione class. Pioglitazone has been shown to be effective and well tolerated in the treatment of patients with type 2 diabetes, as it reduces insulin resistance and improves glycaemic control and abnormal lipid profiles. This double-blind, randomised, placebo-controlled study was conducted for further evaluation of the efficacy and tolerability of once-daily administration of pioglitazone monotherapy alongside dietary measures in patients with type 2 diabetes. Following a 10-week washout period, 251 patients received one of three treatment regimens for 26 weeks: placebo + diet (n = 84), pioglitazone 15 mg once-daily + diet (n = 89), or pioglitazone 30 mg once-daily + diet (n = 78). Pioglitazone, both 15 and 30 mg/day, in addition to dietary control, was associated with significant reductions (vs. placebo) in mean levels of both glycosylated haemoglobin (HbA 1C ) and fasting blood glucose (FBG). HbA 1C was reduced by 0.92 % and 1.05 %, respectively, and FBG was reduced by 34.3 and 36.0 mg/dl, respectively, compared with the control group. Pioglitazone at 15 and 30 mg/day significantly reduced postprandial blood glucose levels at all visits (- 163 and - 165 mg/dl/hour, respectively) compared with an increase of 47.7 mg/dl/hour on placebo. The profile and frequency of adverse events were similar in all treatment groups. These results indicate that pioglitazone monotherapy together with dietary control is both effective and safe in patients with type 2 diabetes.     

Alpha 2-macroglobulin and proliferative retinopathy in type 1 diabetes

Serum alpha 2-macroglobulin (alpha 2m) and total glycosylated haemoglobin (HbA1) concentrations were measured in 110 insulin dependent Type 1 diabetics with minimal or no fundoscopic retinopathy, referred to as non-retinopaths, and in 52 proliferative retinopaths. Proteinuria was recorded in 8 (7%) non-retinopaths and 29 (56%) retinopaths and was accompanied by elevated alpha 2m concentrations in both groups of diabetics but only significantly so in the non-retinopaths. Diabetics without proteinuria showed a significant correlation between alpha 2m concentration and duration of diabetes, HbA1 and age (being higher at extremes of age). Alpha 2m concentrations were significantly higher in retinopaths than in non-retinopaths without proteinuria when allowance was made for the influence of age and duration of diabetes on alpha 2m. This difference may be attributed to the higher HbA, levels found in retinopaths than in non-retinopaths and was no longer evident when account was taken of the prevailing HbA1 concentration in individual patients.     

The markers of inflammation and endothelial dysfunction in correlation with glycated haemoglobin are present in type 2 diabetes mellitus patients but not in their relatives

The aim of this study is to test several biomarkers of inflammation, of endothelial dysfunction, glycated haemoglobin, and their reflection in arterial dilatation, in patients with type 2 diabetes mellitus and in their relatives, in order to demonstrate if relatives present markers as a form of precocious indicators of diabetes mellitus. Individuals between 30 and 55 years of age and without clinical arterial disease were divided in three groups: type 2 diabetes mellitus patients without complications (12 men and 18 women); first degree relatives of type 2 diabetes mellitus (14 men and 20 women); and control individuals (9 men and 16 women). Body composition was measured with a bioelectrical impedance analyzer and endothelial function with an eco-Doppler device. We determined glucose, insulin, C-peptide, glycated haemoglobin, fibrinogen, E-selectin, P-selectin, soluble intercellular cell adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) in plasma. We also studied endothelium independent dilatation and endothelium dependent dilatation. The results: ICAM-1 and VCAM-1 were significantly higher in the diabetic group (237.5+/-43.4 and 692.5+/-168.6 ng/l) than in controls (197.4+/-51.2 and 573.5+/-121.1 ng/l, p=0.011 and 0.013, respectively), but were not higher in the family group (224.5+/-45.2 and 599.8+/-150.4 ng/l). CRP was higher in the diabetic group (3.35+/-3.27 mg/l) than in the other groups (1.28+/-1.29 and 1.61+/-1.54 mg/l, p=0.002) and correlated with glycated haemoglobin. The non-endothelium mediated dilatation was lesser in the diabetic group than in the family group (17.3+/-6.1 vs. 24+/-8, p=0.029) and controls. In conclusion patients with uncomplicated type 2 diabetes, but not their relatives, have biochemical markers of sub-clinical inflammation in relationship with glycated haemoglobin and dysfunction of the endothelial cells markers. In these patients endothelium independent dilatation is more affected than endothelium dependent dilatation.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Insulin adjustment by a diabetes nurse educator improves glucose control in insulin-requiring diabetic patients: a randomized trial

BACKGROUND: Diabetic patients taking insulin often have suboptimal glucose control, and standard methods of health care delivery are ineffective in improving such control. This study was undertaken to determine if insulin adjustment according to advice provided by telephone by a diabetes nurse educator could lead to better glucose control, as indicated by level of glycated hemoglobin (HbA1c). METHODS: The authors conducted a prospective randomized trial involving 46 insulin-requiring diabetic patients who had poor glucose control (HbA1c of 0.085 or more). Eligible patients were those already taking insulin and receiving endocrinologist-directed care through a diabetes centre and whose most recent HbA1c level was 0.085 or higher. The patients were randomly assigned to receive standard care or to have regular telephone contact with a diabetes nurse educator for advice about adjustment of insulin therapy. RESULTS: At baseline there was no statistically significant difference between the 2 groups in terms of HbA1c level (mean [and standard deviation] for standard-care group 0.094 [0.008] and for intervention group 0.096 [0.010]), age, sex, type or duration of diabetes, duration of insulin therapy or complications. After 6 months, the mean HbA1c level in the standard-care group was 0.089 (0.010), which was not significantly different from the mean level at baseline. However, the mean HbA1c level in the intervention group had fallen to 0.078 (0.008), which was significantly lower than both the level at baseline for that group (p < 0.001) and the level for the standard-care group at 6 months (p < 0.01). INTERPRETATION: Insulin adjustment according to advice from a diabetes nurse educator is an effective method of improving glucose control in insulin-requiring diabetic patients.     

Glycated haemoglobin values: problems in assessing blood glucose control in diabetes mellitus.

OBJECTIVE--To see whether two measures of glycated haemoglobin concentration--the haemoglobin A1 (HbA1) value and the haemoglobin A1c (HbA1c) value--assess blood glucose control differently in diabetes. DESIGN--Diabetic patients had glycaemic control assessed on the basis of HbA1 and HbA1c values measured by the same high performance liquid chromatography instrument and on the basis of HbA1 measured by electrophoresis. SETTING--A diabetic outpatient clinic. SUBJECTS--208 diabetic patients and 106 non-diabetic controls. MAIN OUTCOME MEASURES--Glycated haemoglobin concentrations classified according to European guidelines as representing good, borderline, or poor glycaemic control by using standard deviations from a reference mean. RESULTS--Fewer patients were in good control (25;12%) and more poorly controlled (157;75%) as assessed by the HbA1c value compared with both HbA1 assays (39 (19%) and 130 (63%) respectively when using high performance liquid chromatography; 63 (30%) and 74 (36%) when using electrophoresis). The median patient value was 8.0 SD from the reference mean when using HbA1c, 5.9 when using HbA1 measured by the same high performance liquid chromatography method, and 4.1 when using HbA1 measured by electrophoresis. CONCLUSIONS--Large differences exist between HbA1 and HbA1c in the classification of glycaemic control in diabetic patients. The HbA1c value may suggest a patient is at a high risk of long term diabetic complications when the HbA1 value may not. Better standardisation of glycated haemoglobin measurements is advisable.     

Lipid metabolism in patients with insulin dependent diabetes. III. Effect of metabolic control of diabetes on the concentration of some blood serum lipid constituents in patients with insulin dependent diabetes]

The levels of the following blood serum lipid constituents: total cholesterol, triglycerides, phospholipids, HDL-cholesterol, lipoprotein fractions, as well as apolipoproteins AI, AII and B, have been determined in patients with insulin-dependent diabetes lasting from 3 months to 15 years in relation to the degree of metabolic control characterized by the levels of fructosamine and glycosylated hemoglobin HbA1c. The group of patients having the level of HbA1c exceeding 10% was characterized by significantly higher levels of cholesterol, triglycerides and Apo-B, and lower content of alpha-lipoprotein as compared to the group with HbA1c level beneath 10%. When fructosamine concentration was considered as an index of metabolic control of diabetes, it was found that the levels of cholesterol, phospholipids and apolipoproteins apo-A and apo-AI are highest in the group with the poor metabolic control and differ significantly from the respective values found in patients with mediocre and good metabolic control. Considering biological role of the individual lipids and lipoproteins, it should be stressed that the proper control of glycaemia is important for preventing the development of atherosclerosis in patients with insulin-dependent diabetes.     

Glycated Hemoglobin,Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers’ Health Study Baseline

Background and Aims

Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome.

Methods

We used baseline data from 3200 non-diabetic male participants in the Aragon Workers'' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI).

Results

Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering.

Conclusions

HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.     

安立泽联合胰岛素治疗单独胰岛素降糖欠佳的高龄2型糖尿病患者临床观察

目的：观察安立泽应用于单独胰岛素治疗血糖控制欠佳的高龄2型糖尿病患者的疗效及安全性。方法：200例高龄2型糖尿病胰岛素降糖欠佳的患者（空腹血糖控制在7．8．13．9mmol／L范围内）,随机分成对照组和治疗组,对照组采用胰岛素加安慰剂治疗80例;治疗组120例,分为A、B、c三组,每组40例,A、B、c三组分别在继续应用胰岛素治疗的基础上加服安立泽4mg／d、5mg／d、6mg／d,疗程三个月。观测治疗组和对照组治疗前后FPG及PPG、HbAlC、BMI和胰岛素用量的改变及治疗的安全性。结果：对照组和治疗组治疗前的各指标无明显差异（P〉0．05）;A、B、c三组在治疗后1个月和3个月FPG、PPG、H1）A1C均有明显的下降（P〈0．05,P〈0．01）,而对照组治疗前后FIG、PPG、HbAlC略有下降,差异不明显（P〉0．05）;A、B、c三组胰岛素的用量及体重指数较治疗前均略有下降,三组间无显著性差异;对照组和治疗组的不良反应发生率无显著差异。结论：对高龄2型糖尿病单用胰岛素治疗血糖控制欠佳的患者,加用安立泽治疗,可使糖尿病相关指标得以良好的控制,减少糖尿病患者每日胰岛素用量,临床毒副作用较小。     

Beta cell response to a mixed meal in nigerian patients with type 2 diabetes

ABSTRACT: BACKGROUND: The pathophysiology of type2 diabetes involves both insulin resistance and poor beta cell function. Studies have been done in several populations to assess the relative importance of these mechanisms in individual patients. In our environment studies to assess beta cell function have been done with glucagon stimulation or an oral glucose tolerance test. This study was done to assess the response of the beta cell to a standardized mixed meal and its relationship with glycaemic control in patients with type2 diabetes. METHODS: Ninety patients with type 2 diabetes were recruited into the study. Weight, height, body mass index and waist circumference were measured. Blood samples were analysed for fasting plasma glucose (FPG) and fasting C peptide (FCP) and glycated haemoglobin (HbA1c). Patients were given their usual drugs for management of their diabetes and then served with a standard meal calculated to contain 50 g of carbohydrate, made up of 53 % carbohydrate, 17 % of protein and 30 % of lipids, providing 500 kcal. Blood samples 2 hours after the start of the meal were analysed for postprandial glucose (PPG) and postprandial C peptide (PCP). Fasting (M0) and postprandial beta cell responsiveness (M1) were calculated. RESULTS: The mean FPG and PPG were 7.51+/ 3.39 mmol/l and 11.02+/4.03 mmol/l respectively while the mean glycated haemoglobin (HbA1c) was 9.0+/2.5 %. The mean fasting C peptide was 1.44+/1.80ug/ml. Many of the patients (56.7 %) had low FCP levels. The mean postprandial C peptide was 4.0+/2.8 ng/ml. There were significant correlations between M1, HbA1c and PPG (p = 0.015, 0.024, 0.001 respectively) and also between M0, HbA1c, PPG and FPG (p = 0.001, 0.002, 0.001). HbA1c decreased across increasing tertiles of M0 (p < 0.001) and also M1 (p = 0.002). In step-wise linear regression analysis, M0 and M1 significantly predicted HbA1c. CONCLUSIONS: Many of the patients had low C peptide levels with poor beta cell response to the meal. The patients had poor glycaemic control and poor beta cell function. Both fasting and postprandial beta cell responsiveness were significant determinants of blood glucose and glycated haemoglobin levels. It is likely that putting these patients on insulin may have led to better glycaemic control in them.     

Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes.

OBJECTIVE--To ascertain which factors determine the progression from very low rates of albumin excretion to persistent microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN--A 10 year prospective study of a cohort of diabetic patients. SETTING--Outpatient department of the Portsmouth District Hospitals. SUBJECTS--97 patients with insulin dependent diabetes mellitus who were initially free of microalbuminuria and hypertension. MAIN OUTCOME MEASURE--Urinary albumin: creatinine ratio. RESULTS--Eight of the 97 patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3 mg/mmol in three consecutive early morning samples) by the 10 year follow up. The group who developed microalbuminuria had higher baseline log10 plasma glucose concentrations (mean (SD), 1.210 (0.122) v 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) v 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) v 15.6 (7.8) years, P < 0.05). There was no difference in baseline duration of diabetes, smoking, sex, insulin dose, body mass index, serum creatinine concentration, or systolic, diastolic, or mean arterial blood pressure between the two groups. Multiple linear regression analysis showed that urinary albumin:creatinine ratio at 10 years was influenced by initial albumin:creatinine ratio (P = 0.006), initial glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P = 0.045). Genotype for angiotensin converting enzyme was not related to the development of microalbuminuria nor, in a larger group of patients, the presence of any degree of diabetic nephropathy. CONCLUSION--In patients with insulin dependent diabetes mellitus the progression of minimal albuminuria and the development of microalbuminuria is determined primarily by poor long term glycaemic control. There is a weaker relation with longer duration of disease and younger age at onset of diabetes, but blood pressure does not seem to be implicated. Gene polymorphism for angiotensin converting enzyme is not linked to the development of microalbuminuria or established diabetic nephropathy.     

Metabolic control of diabetes in general practice clinics: comparison with a hospital clinic.

An assessment was made of the degree of metabolic control achieved in diabetic patients attending mini clinics run by general practitioners compared with that in matched diabetic patients attending a hospital clinic. Patients were grouped according to whether they were being treated with diet alone, an oral hypoglycaemic, insulin once daily, or insulin twice daily. Statistical analysis showed no significant difference between patients attending mini clinics and those attending the hospital clinic in retrospective mean blood glucose, retrospective mean glycosylated haemoglobin (HbA1), or prospective HbA1 concentrations. General practitioners providing diabetic care on an organised basis can achieve a degree of glycaemic control in diabetic patients equal to that reached by a hospital clinic.     

How best to use partial meal replacement in managing overweight or obese patients with poorly controlled type 2 diabetes

Objective:

To compare patient compliance and benefits, over 12 months, of 1 versus 2 partial meal replacement (PMR) for the management of overweight/obese subjects with inadequately controlled type 2 diabetes.

Design and Methods:

Thirty‐six overweight patients with inadequately controlled type 2 diabetes (BMI > 27 kg/m² and HbA1c > 7.5% [58 mmol/mol]) were randomized to receive 1 or 2 PMR/day, while maintaining usual lifestyle. Subjects were seen monthly and adjustment of medications was made to prevent hypoglycemia. Compliance was assessed by counting unused sachets.

Results:

Patients on 2 PMR/day lost almost 4 kg compared with only 0.5 kg in the 1 PMR/day group. This difference was statistically significant (P < 0.05). Overall PMR was about 30% as effective as in our previous study on total meal replacement. Reductions in weight, waist, and HbA1c were better in the 2 PMR/day group while patient dropout and compliance were not worse over a 12‐month period.

Conclusion:

PMR provides a further management option for overweight/obese individuals with type 2 diabetes. The initial recommendation should be 2 PMR/day.     

A randomised,open-labelstudy of insulin glargine or neutral protamine Hagedorn insulin in Chinese paediatric patients with type 1 diabetes mellitus

Background

We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy.

Methods

This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131).

Results

In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean?±?SD of absolute change in HbA1c was–0.25?±?1.68% (–2.69?±?18.32 mmol/mol) in the insulin glargine group and –0.54?±?1.67% (–5.55?±?20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3?±?45.8 versus32.3?±?43.2); severe hypoglycaemia was rare (<2%).

Conclusions

Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.