Pregnancy in women with Type 2 diabetes: who takes metformin and what is the outcome?

AIMS: To review pregnancy outcomes in women with Type 2 diabetes (Type 2 DM), comparing women treated with those not treated with metformin. METHODS: Data were collected by case-note review for all pregnancies in women with Type 2 DM over a 6-year period (1998-2003) at the National Women's Hospital. Two hundred and fourteen pregnancies were included, metformin was taken in 93 pregnancies and continued until delivery in 32; the remaining 121 pregnancies comprised the control group. The principal outcome measures were preeclampsia, perinatal loss and neonatal morbidity. RESULTS: Baseline characteristics differed between groups: women in the metformin group had greater mean (SD) body mass index [35.5(7.6) vs. 33.5(6.6) kg/m2, P < 0.05], more chronic hypertension (19% vs. 7%, P < 0.05) and higher mean (SD) first trimester glycated haemoglobin (HbA1c) levels [8.3(1.9)% vs. 7.5(1.7)%, P < 0.005]. There was no difference between metformin and control groups, respectively, in the rate of preeclampsia (13% vs. 14%, P = 0.84), perinatal loss (3% vs. 2%, P = 0.65) or neonatal morbidity, including rate of prematurity (23% vs. 22%, P = 0.7), admission to the neonatal unit (40% vs. 48%, P = 0.27), respiratory distress (9% vs. 18%, P = 0.07) and treatment with intravenous dextrose (20% vs. 31%, P = 0.08). CONCLUSIONS: Pregnant women with Type 2 DM who were treated with metformin had more risk factors for adverse pregnancy outcomes, but no differences in outcomes were seen compared with women not taking metformin. We need randomized trials to address potential benefits of metformin treatment in this population that may be masked by current practice.     

HbA1c in healthy, pregnant women

AIM: Congenital malformations and macrosomia in infants of women with type 1 diabetes mellitus (DM1) still occur, even if diabetic control is considered 'good' (i.e. HbA1c below the nonpregnant upper reference value of 6.3%). We, therefore, measured HbA1c in healthy, pregnant women to determine whether the upper reference value for pregnant women should be lower than the nonpregnant value. METHODS: We investigated HbA1c, measured by high-performance liquid chromatography (HPLC), in two groups of healthy primigravid women. Group 1 (n=30; 30.0 +/- 5.3 (mean +/- sd) years; body mass index (BMI) before pregnancy 21.7 +/- 5.3 kg/m2) had a gestational age of 30 weeks (34.6 +/- 2.5) pregnant. None of the women had diabetes in the family in the first and/or second degree. RESULTS: Group 1 had an HbA1c of 4.3 +/- 0.3% (range 3.9-5.0) and in group 2 the HbA1c was 4.7 +/- 0.4% (range 3.6-5.9) (p < 0.001). No relation was found between HbA1C and BMI vs birth weight, corrected for gestational age, within the groups. CONCLUSIONS: Healthy, pregnant women had a low HbA1C, particularly in the first trimester of pregnancy. This might implicate that for prevention of congenital malformations and macrosomia in pregnant DM1 women and HbA1C should be below 5% in the first trimester of pregnancy and below 6% in the third trimester.     

Long-term mortality and incidence of renal dialysis and transplantation in type 1 diabetes mellitus

AIMS: We investigated long-term mortality and requirement of renal replacement therapy (RRT) in type 1 diabetes mellitus (T1DM) to study risk factors and late complication incidence of T1DM in a prospective cohort study at Lainz Hospital, Vienna, Austria. METHODS: In 1983-1984, T1DM patients [n = 648; 47% females, 53% males; age, 30 +/- 11 yr; T1DM duration, 15 +/- 9 yr; body mass index, 24 +/- 4 kg/m(2); glycated hemoglobin (HbA1c), 7.6 +/- 1.6%] were stratified into HbA1c quartiles [1st, 5.9 +/- 0.5% (range, 4.2-6.5%); 2nd, 6.9 +/- 0.3% (6.6-7.4%); 3rd, 7.9 +/- 0.3% (7.5-8.4%); and 4th, 9.6 +/- 1.3% (8.5-14.8%)]. Twenty years later, both endpoints (death and RRT) were investigated by record linkage with national registries. RESULTS: At baseline, creatinine clearance, blood pressure, and body mass index were comparable among the HbA1c quartiles, whereas albuminuria was more frequent in the 4th quartile (+15%; P < 0.03). After the 20-yr follow-up, 13.0% of the patients had died [rate, 708 per 100,000 person-years (95% confidence interval, 557-859)], and 5.6% had received RRT [311 per 100,000 person-years (95% confidence interval, 210-412)]. Patients with the highest HbA1c values (4th quartile) had a higher mortality rate and a greater incidence of RRT (P < 0.04). In the Cox proportional hazards analysis, age, male gender, increased HbA1c, albuminuria, and reduced creatinine clearance were predictors of mortality (P < 0.05). Predictors of RRT were albuminuria (P < 0.001), reduced creatinine clearance (P < 0.001), and belonging to the 4th HbA1c quartile (P = 0.06). In Kaplan-Meier analysis, mortality was linearly associated with poor glycemia, whereas RRT incidence appeared to rise at a HbA1c threshold of approximately 8.5%. CONCLUSION/INTERPRETATION: In the Lainz T1DM cohort, 13.0% mortality and 5.6% RRT were directly associated with and more frequently found in poor glycemia, showing that good glycemic control is essential for the longevity and quality of life in T1DM.     

Severe hypoglycaemia during pregnancy in women with Type 1 diabetes is common and planning pregnancy does not decrease the risk

Aims The aim of this study was to identify risk factors for severe hypoglycaemia (SH) in pregnancy in Type 1 diabetes, including associations with pregnancy planning and glycaemic control. Methods Clinical data including details of the pregnancy and its outcome, glycaemic control, frequency of SH and evidence of pregnancy planning were collected prospectively as part of a national audit of 160 pregnancies in women with Type 1 diabetes. Results An episode of SH was experienced by 29.4% of women at some point during the pregnancy, with the percentage of women experiencing SH decreasing from 21.9% in the first trimester to 18.1% in trimester 2 and 10.9% in trimester 3. Longer duration of diabetes was associated with increased frequency of SH during pregnancy (r = 0.191, P = 0.012). A greater fall in glycated haemoglobin (HbA_1c) between pre‐pregnancy and the first trimester was not associated with increased risk of SH in trimester 1. Planned pregnancies had better glycaemic control but higher risk of SH in trimester 1 (P = 0.047). Women with pre‐pregnancy retinopathy and current smokers had an increased risk of SH in trimester 3 (P = 0.029, P = 0.033). Conclusions SH is common during pregnancy and particularly in the first trimester. Planning pregnancy does not decrease the risk of SH. Improvements in glycaemic control at the start of pregnancy do not appear to increase the risk of SH. Education of women and their partners about the risks of SH and its management is essential when planning pregnancy.     

Birthweight of Babies Born to Mothers with Type 1 Diabetes: is it Related to Blood Glucose Control in the First Trimester?

A retrospective study of 133 pregnancies in women with Type 1 diabetes was performed, and the 116 which progressed beyond 28 weeks were further analysed. Despite good maternal blood glucose control (mean (+/- SE) HbA1 levels 8.6 +/- 0.2% at the end of the first trimester; 6.9 +/- 0.2% at delivery; normal range 4.0-8.5%), 38% of babies had birthweights above the 90th centile and operative intervention occurred in 77 deliveries (66%). There was no significant correlation between birthweight and HbA1 level at any stage of pregnancy, but mothers with babies above the 90th centile for weight had a higher HbA1 at the end of the first trimester than mothers with babies below the 90th centile (9.3 +/- 0.5 vs 7.9 +/- 0.2%, p less than 0.05). In contrast there was no difference in the HbA1 levels at delivery (7.0 +/- 0.3 vs 6.8 +/- 0.2%). The perinatal mortality rate was 17.7 per 1000 births. The results confirm that in Type 1 diabetes large babies are common despite good blood glucose control, and suggest that maternal blood glucose control in the first trimester may be an important determinant of birthweight.     

Diabetic pregnancy: outpatient follow-up in a Brazilian University Hospital

In this study we assessed neonatal complications of diabetic in 50 pregnant women at a University Hospital during 2001-2002: 13 (26%) with type 1 diabetes (DM1), 16 with DM2, and 21 (42%) with gestational DM (GDM). The mean outpatient follow-up was at 16.3+/-8 wk for patients with DM1, 22.9+/-7.5 wk for DM2, and 26.0+/-8.9 wk for GDM. Mean HbA1c, fasting and 2-h post-prandial glycemia on first attendance were respectively: 6.1+/-1,1% (RV: 2.6-6.2%), 132+/-39 mg/dL and 190+/-54 mg/dL. 22 patients were on insulin and 15 were on oral antidiabetic agents (OA) at first evaluation. OA were taken on conception and during the first pregnancy trimester and no malformations were seen in the children. Their metabolic profile was similar to other pregnant women. Caesarean section was needed in 54.5% of deliveries. Complications: 56.1% were macrosomic babies, with a mean fetal weight of 3.48+/-0.73 Kg, with no differences according to treatment (insulin vs. OA). We conclude that diabetic pregnant women begin their prenatal care at a later period, often taking OA that are not officially advised to be used during pregnancy and are not in a regular metabolic control. As a result, they have macrosomic infants. Even though we have found no complications related to the OA use during pregnancy, we should not encourage their use until more safety studies are available.     

Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control.

OBJECTIVES: This study was designed to determine whether blood thrombogenicity is related to chronic glycemic control in type 2 diabetes mellitus (T2DM). BACKGROUND: Type 2 diabetes mellitus is associated with accelerated atherosclerosis and a high rate of arterial thrombotic complications. Whether increased blood thrombogenicity is associated with glycemic control has not been properly tested. METHODS: Forty patients with T2DM with hemoglobin A1c (HbA1c) > or =7.5% were selected. Maintaining their current hypoglycemic therapies, patients were randomized into a conservative (diet modification plus placebo) or intensive (diet modification plus troglitazone) hypoglycemic regimen for three months. Blood thrombogenicity was measured at baseline and after three months with the Badimon ex vivo perfusion chamber and assessed as platelet-thrombus formation. The repeated measurements allowed every patient to be his/her own control. RESULTS: Patients in both groups (48% and 74% of the conservative and intensive groups, respectively) improved glucose control (HbA1c reduction > or =0.5%), showing a significant decrease in blood thrombogenicity. A significant positive correlation was observed between the reduction in thrombus formation and the reduction in HbA1c (r = 0.47, p < 0.01). The reduction in HbA1c achieved by both treatments was comparable. Patients without glycemic improvement showed no change in blood thrombogenicity. Improved glycemic control was the only significant predictor of a decrease in blood thrombogenicity. CONCLUSIONS: In T2DM, there is an association between improved glycemic control and blood thrombogenicity reduction. The effect of glycemic control on the thrombotic complications of T2DM patients deserves further investigation.     

老年2型糖尿病患者动态血糖监测分析

目的 探讨老年2型糖尿病患者的动态血糖波动特点.方法 对老年2型糖尿病患者(老年组)92例和中青年2型糖尿病患者(中青年组)58例进行动态血糖监测,对比分析两组患者血糖谱特征及老年不同糖化血红蛋白(HbA1c)水平糖尿病患者的血糖谱特征.结果 (1)老年组与中青年组比较,血糖波动系数(BGFC)增大[(2.68±1.00)mmol/L对(2.12±0.74) mmol/L,t=-3.691,P＜0.001];餐后血糖漂移幅度(PPGE)增大,早餐后分别为 ( 5.96±2.47) mmol/L对(5.11±2.44) mmol/L(t=-2.058,P＜0.05),晚餐后分别为(5.17±2.15) mmol/L对 (4.16±2.28) mmol/L(t=-2.730,P＜0.01);餐后血糖达峰时间延长,早餐后(112.5±29.7) min对(97.0±27.2) min(t=-3.225,P＜0.01),中餐后(140.0±39.7)min对 (118.1±42.6) min(t=-3.195,P＜0.01);低血糖发生频率增加(26.3%对5.5%,P＜0.05);最大血糖漂移幅度(LAGE)增大,分别为(9.66±2.48) mmol/L对(8.40±3.13) mmol/L(t=-2.720,P＜0.01);(2)老年组患者随HbA1c下降,低血糖发生率增加(P＜0.05);随 HbA1c升高,血糖波动幅度增大;(3)HbA1c与空腹血糖(FBG)、日平均血糖(MBG)、高血糖时间比(PT7.8、PT11.1)、最低血糖(LBG)、最高血糖(HBG)、BGFC、PPGE、LAGE均正相关(r=0.899～0.289,均P＜0.001);逐步回归分析显示,MBG、FBG、PT7.8与HbA1c独立相关(校正的R2=0.807,P＜0.05).结论 老年2型糖尿病患者血糖波动幅度大,易发生餐后高血糖和夜间低血糖,动态血糖监测能较详细地显示患者的血糖水平及波动特征.

Abstract：

Objective To investigate the characteristics of the blood glucose fluctuation in elderly patients with type 2 diabetes mellitus (T2DM). Methods The 92 elderly patients with T2DM (the elderly group) and 58 young and middle-aged patients with T2DM (the non-elderly group) were monitored using the continuous glucose monitoring system(CGMS). The characteristics of glucose profiles of the two different age groups, and of the different glycosylated hemoglobin (HbA1c) level groups in the elderly were comparatively analyzed. Results (1)There was no significant difference in HbA1c level between the elderly group and the non-elderly group. Compared with the non-elderly group, the elderly group showed the increases in blood glucose fluctuant coefficient [BGFC, (2.68±1.00) mmol/L vs. (2.12±0.74) mmol/L, t=-3.691, P＜0.001], in postprandial glucose excursion (PPGE) of breakfast and supper [(5.96±2.47) mmol/L vs. (5.11±2.44) mmol/L, t=-2.058, P＜0.05; (5.17±2.15) mmol/L vs. (4.16±2.28) mmol/L, t=-2.730, P＜0.01], in the time to postprandial glucose peak of breakfast and lunch [(112.5±29.7) min vs. (97.0±27.2) min, t=-3.225, P＜0.01; (140.0±39.7) min vs. (118.1±42.6) min, t=-3.195, P＜0.01], in the frequency of hypoglycemia (26.3% vs. 5.5%, P＜0.05), and showed the largest amplitude of glycemic excursions [LAGE, (9.66±2.48) mmol/L vs.(8.40±3.13) mmol/L, t=-2.720, P＜0.01]. (2)In the elderly, along with decreased HbA1c, the incidence of hypoglycaemia increased (P＜0.05); And along with increased HbA1c, the amplitude of blood glucose fluctuation increased. There were significant differences in BGFC, PPGE of breakfast and lunch, and LAGE among different HbA1c level groups (P＜0.01, P＜0.05, P＜0.05, P＜0.001). (3)HbA1c was positively correlated with FBG, mean blood glucose (MBG), percentage of time at glycemia (PT7.8, PT11.1), the lowest blood glucose (LBG), the highest blood glucose (HBG), BGFC, PPGE and LAGE (r=0.899-0.289, all P＜0.001). Multiple stepwise regression analysis indicated that MBG, FBG and PT7.8 was the independent influential factor of HbA1c (adjusted R2=0.807, P＜0.05). Conclusions The elderly patients with T2DM are at a particularly high risk for postprandial hyperglycemia and nocturnal hypoglycemic episodes, CGMS could show glucose fluctuation characters of T2DM patients diurnally, and provide a clinical basis for reasonable therapy.     

The relationship between glycemic control and platelet activity in type 2 diabetes mellitus

AimsPlatelet activity and aggregation potential, which are essential components of thrombogenesis and atherosclerosis, can be conveniently estimated by measuring mean platelet volume (MPV) as part of whole blood count. It has been shown that MPV was significantly higher in diabetes mellitus (DM); however, the effect of glycemic control on MPV has not been studied. The aim of this study was to investigate the relationship among MPV, glycemic control, and micro- and macrovascular complications in type 2 DM.MethodsSeventy patients with type 2 DM and 40 age- and sex-matched healthy individuals were enrolled. Diabetic patients were grouped into those with glycated hemoglobin (HbA1c) levels ≤7% (Group A, n=35 patients) and those with HbA1c >7% (Group B, n=35 patients). Initially, both groups were compared with regard to MPV, HbA1c, serum lipid levels, coronary artery disease, retinopathy, neuropathy, and nephropathy. Thereafter, Group B was called to monthly visits to obtain improved control glycemic control, which was defined as achievement of HbA1c ≤7%. At the end of 3 months of follow-up, Group B was reevaluated.ResultsMPV was significantly higher in patients with DM than in controls (8.7±0.8 fl vs. 8.2±0.7 fl, P=.002). In diabetic patients, there was a significant positive correlation between MPV and HbA1c levels (r=.39, P=.001) but not diabetic vascular complications. When we compared the two diabetic groups, Group B patients had significantly higher MPV than Group A (9.0±0.7 fl vs. 8.4±0.8 fl, P=.01). Thirty patients (86%) of Group B achieved improved glycemic control at the end of the 3 months. MPV of the patients with improved glycemic control were significantly decreased compared to baseline MPV (8.4±0.8 fl vs. 9.0±0.7 fl, P=.003).ConclusionsOur results suggested a close relationship between poor glycemic control and increased platelet activity in patients with type 2 DM. Furthermore, platelet activity recovered through improved glycemic control, which may prevent the possible role of platelets in cardiovascular events in these patients.     

An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet

Our first specific aim in an observational study of 431 nondiabetic women with polycystic ovary syndrome (PCOS), aged >or=20 years and with >or=11 months follow-up on metformin diet, was to prospectively assess relationships between pretreatment glucose and insulin resistance (IR) and the development of type 2 diabetes mellitus (T2DM) or gestational diabetes (GD). Our second specific aim was to determine whether development of T2DM and GD was independently associated with lesser reduction of IR on metformin diet when compared with women who remained free of T2DM and GD. Women with body mass index <25 kg/m(2) and those with body mass index >or=25 kg/m(2) were, respectively, instructed in a 2000- or 1500-cal/d, high-protein (26% of calories), low-carbohydrate (44%) diet, with 30% of calories as fat and a polyunsaturate-saturate ratio of 2:1. Three groups of women with PCOS were categorized: (a) 17 with no previous GD, who developed T2DM on metformin diet (mean +/- SD follow-up, 49 +/- 33 months), (b) 401 with no previous GD and free of T2DM on metformin diet (follow-up, 38 +/- 25 months), and (c) 13 with either previous GD or GD on metformin diet (follow-up, 38 +/- 25 months). On metformin diet, women who developed T2DM vs those who remained free of T2DM had higher pretreatment glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.16; P = .003) and homeostasis model assessment of insulin resistance (HOMA-IR) (OR, 1.22; 95% CI, 1.04-1.42; P = .01), and less reduction of HOMA-IR (OR, 0.82; 95% CI, 0.72-0.92; P = .0008). On metformin diet, women either with previous GD or who developed GD vs those who remained free of T2DM had less reduction of HOMA-IR (OR, 0.88; 95% CI, 0.78-0.99; P = .03). By repeated-measures analysis, on metformin diet, women who did not develop T2DM had reduction in HOMA-IR (P < .0001), with the slope of this curve different (P = .002) from the unchanged IR exhibited by women who developed T2DM and different (P = .017) from an increased IR slope (P = .049) in women who had GD. In women with PCOS, pretreatment glucose and IR, and lesser reduction in IR on metformin diet were associated with T2DM and GD.     

Sex-influenced association between free triiodothyronine levels and poor glycemic control in euthyroid patients with type 2 diabetes mellitus

ObjectiveThe study investigated the association between free triiodothyronine (FT3) and poor glycemic control with different definitions in euthyroid patients with type 2 diabetes mellitus (T2DM).MethodsThis was a cross-sectional study which included 2172 patients from National Metabolic Management Center in Ruijin Hospital. The association between thyroid function and glycated hemoglobin A1c (HbA1c) was determined by multiple liner regression models. The association between FT3 and poor glycemic control was further determined by binary logistic regression models. Two definitions of poor glycemic control (HbA1c ≥ 7% and HbA1c ≥ 8%) were applied when we analyzed the association.ResultsPrevalence of HbA1c ≥ 7% and HbA1c ≥ 8% were 63.8% and 39.3%, respectively. After adjusting for confounding factors, FT3, rather than free tetraiodothyronine (FT4) or thyroid stimulating hormone (TSH), was independently associated with HbA1c (β = −0.104, P = 0.002). Further analysis after gender stratification showed that the association was only found in males (β = −0.164, P < 0.001). We further analyzed the association between FT3 quartiles and poor glycemic control. FT3 quartiles were not significantly associated with the risk of HbA1c ≥ 7% before and after adjusting for confounding factors in both genders. FT3 quartiles were negatively associated with the risk of HbA1c ≥ 8% only in males, independent of traditional risk factors for poor glycemic control (P for trend = 0.030).ConclusionsFT3 in the reference range was significantly associated with reduced risk of HbA1c ≥ 8% in males, independent of traditional risk factors for poor glycemic control.     

Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data

The optimization of metabolic control in Type 1 and Type 2 diabetes mellitus (T1DM and T2DM, respectively) [i.e., the maintenance of near-normal hemoglobin A(1c) (HbA(1c)) without increasing the risk of hypoglycemia] could be enhanced by analysis of self-monitoring blood glucose (SMBG) data assessing complementary processes: exposure to hyperglycemia and hypoglycemia. We present algorithms that simultaneously estimate HbA(1)c and risk for significant hypoglycemia using 45-60 days of SMBG. The algorithms were developed using a primary data for 96 subjects with T1DM (n = 48) and T2DM, and were validated in an external data for 520 subjects with T1DM (n = 231) and T2DM. All subjects were on insulin. In the primary (external) data the estimation of HbA(1c) had absolute error of 0.5 (0.7) units of HbA(1c) and percent error of 6.8% (8.1%); 96% (96%) of all estimates were within 20% from reference HbA(1c). The SMBG-estimated value of HbA(1c) was closer to current reference HbA(1c) than a reference HbA(1c) value taken only 2-3 months ago. The results in T1DM and T2DM were similar. Linear model predicted future significant hypoglycemia (R(2) = 62%, p < 0.0001). The leading predictor was a previously introduced Low Blood Glucose Index, which alone had R(2) = 55%. Probability model assessed accurately the odds for future moderate/severe hypoglycemia (coefficients of determination 92%/94%). Four risk categories were identified; within moderate- and high-risk category, there was no difference between T1DM and T2DM in the occurrence of prospective significant hypoglycemia. SMBG data allow for accurate estimation of the two most important markers of metabolic control in T1DM and T2DM - HbA(1c) and risk for hypoglycemia.     

Impairment of left and right ventricular longitudinal strain in asymptomatic children with type 1 diabetes

AimThe relationship between type 1 diabetes (T1DM) and cardiac function in children is not well established. The purpose of this study was to investigate whether children and adolescents with T1DM present early asymptomatic abnormalities of left ventricular (LV) and right ventricular (RV) function. In addition, we evaluated the relationship of any such abnormalities with glycemic control and diabetes duration.MethodsThis was a prospective study. Standard echocardiography, tissue Doppler imaging, and two-dimensional strain analysis were performed prospectively in 52 children with T1DM. The results were compared with those from 52 healthy children matched for age and sex.ResultsThere were no significant differences between the two groups in LV ejection fraction or RV systolic function. There was a difference between the two study groups in transtricuspid flow: the E-wave and A-wave velocities were significantly higher in the diabetic group. Left ventricular global longitudinal strain (LV GLS) was significantly lower in children with T1DM (?20.01 ± 1.86% vs. ?22.99 ± 0.98%, respectively; P < .001), as was RV free-wall longitudinal strain (RV FWLS) (?29.13 ± 1.85% vs. ?30.22 ± 1.53%, respectively; P = .002). LV GLS was correlated with diabetes duration (r = 0.444, P < .001) and glycated hemoglobin (HbA1c) (r = 0.683, P < .001); however, no correlation was found between RV FWLS and HbA1c or diabetes duration.ConclusionsOur findings suggest that LV GLS and RV FWLS are impaired in children with T1DM and that the decrease in LV GLS is correlated with diabetes duration and HbA1c levels.     

The efficacy and safety of the dipeptidyl peptidase-4 inhibitor saxagliptin in treatment-naive patients with type 2 diabetes mellitus: a randomized controlled trial

ABSTRACT: BACKGROUND: The aim of this study was to assess efficacy and safety of saxagliptin monotherapy for up to 76 weeks in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control, with main efficacy assessment at 24 weeks. METHODS: 365 treatment-naive patients with T2DM (HbA1c 7.0%-10.0%) were treated with saxagliptin 2.5 mg q.A.M., saxagliptin 2.5 mg q.A.M. with possible titration to saxagliptin 5 mg, saxagliptin 5 mg q.A.M., saxagliptin 5 mg q.P.M., or placebo. After week 24, patients in all groups were eligible for titration to saxagliptin 10 mg based on HbA1c [greater than or equal to]7%, and all unrescued placebo patients began blinded metformin 500 mg/day. Rescue with open-label metformin was available for patients with inadequate glycemic control. RESULTS: At week 24, placebo-subtracted mean HbA1c reduction from baseline (LOCF) was significantly greater in the saxagliptin treatment groups vs placebo, and remained greater through week 76. Serious adverse events (AEs) and discontinuations due to AEs were similar in saxagliptin and control groups; incidence of confirmed hypoglycemia was low across all treatment groups (saxagliptin-treated, 2 [0.7]; control, 1 [1.4]). CONCLUSIONS: In treatment-naive patients with T2DM, saxagliptin monotherapy demonstrated statistically significant improvement in HbA1c compared with placebo at 24 weeks and was generally well tolerated for up to 76 weeks. Trial registration ClinicalTrials.gov Identifier: NCT00316082.     

Comparison of annual variability in HbA1c and glycated albumin in patients with type 1 vs. type 2 diabetes mellitus

ObjectiveIt has been suggested that plasma glucose (PG) levels per se and long-term variations in PG levels are associated with diabetic vascular complications. Glycated albumin (GA) reflects shorter-term glycemic control, as well as postprandial PG levels, as compared to HbA1c. In this study, we hypothesized that GA more strongly reflects long-term variations in PG levels than HbA1c, and compared the variability of HbA1c and that of GA in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).MethodsThis study included 8 T1DM patients and 48 T2DM patients. Over a 1-year period, HbA1c and GA were measured every month and the mean values and coefficients of variation (CV) for each patient were calculated.ResultsIn both T1DM and T2DM patients, the CV of GA was significantly higher than the CV of HbA1c. Both the CV of HbA1c and the CV of GA were significantly higher in the T1DM patients than in the T2DM patients.ConclusionThe annual variability in GA was greater than that in HbA1c. In addition, the annual variability in HbA1c and that in GA in the T1DM patients were greater than in the T2DM patients. Our findings suggest that GA more accurately reflects long-term variations in PG levels than HbA1c.     

The pregnancies of women with Type 2 diabetes: poor outcomes but opportunities for improvement.

AIM: To compare the outcomes of Type 1 and Type 2 diabetic pregnancies and identify risk factors for poor outcome of Type 2 pregnancies METHODS: The data from all (389 Type 1 and 146 Type 2) pre-gestational diabetic pregnancies from 10 UK hospitals were collected prospectively. RESULTS: The Type 2 mothers were less likely to have documented pre-pregnancy counselling (28.7 vs. 40.5%; P<0.05) or be taking folic acid at conception (21.9 vs. 36.4%; P<0.001) than Type 1 mothers. The percentage of pregnancies having a serious adverse outcome was higher in Type 2 patients (16.4 vs. 6.4%; P=0.002). Congenital abnormalities (12.3% in Type 2 vs. 4.4% in Type 1; P=0.002) accounted for most of this difference. The HbA1c of the Type 2 patients was similar to that of the Type 1 with mean first trimester HbA1c of 7.22 and 7.35%, respectively (P=0.5). Treatment with oral hypoglycaemic agents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.3; P=0.04], body mass index (OR, 1.09; 95% CI, 1.01-1.18; P=0.02) and folic acid supplementation (OR, 0.3; 95% CI, 0.09-1.0; P=0.04) were all independently associated with congenital malformation. CONCLUSION: Type 2 diabetic pregnancies are characterized by poor pre-pregnancy planning, inadequate folic acid supplementation and treatment with oral hypoglycaemic agents, all of which may contribute to the serious adverse outcomes affecting one in six Type 2 diabetic pregnancies. These remediable aspects of the pre-pregnancy care of women with Type 2 diabetes provide opportunities for improving the outcome towards that of women with Type 1 diabetes.     

老年2型糖尿病患者HRV与下肢动脉病变相关性分析(英文)

目的:探讨老年2型糖尿病患者心率变异性(HRV)与下肢动脉病变(LEAD)的关系及其临床意义。方法:选择老年糖尿病患者65例。根据下肢病变情况分为糖尿病合并下肢动脉病变组(LEAD组,36例)、糖尿病无下肢动脉病变组(NLEAD组,29例),另设正常对照组(23例),进行24h动态心电图检查,测定心率变异各指标;同时检测各组血压,糖、脂代谢指标,CRP,血浆脂联素等指标,进行相关及多元Logistic回归分析。结果:(1)糖尿病两组患者的SBP、HbA1c、LDL-C、CRP均显著高于正常对照组(P0.05),与NLEAD组比较,LEAD组病程[(3.00±2.00)年比(7.50±4.00)年]、SBP[(140.24±8.95)mmHg比(147.61±7.58)mmHg]、HbA1c[(6.40±0.70)%比(7.15±2.05)%]、血浆纤维蛋白原(Fg)[(2.57±0.51)g/L比(3.02±0.71)g/L]、LDL-C[(2.27±0.50)mmol/L比(2.81±0.71)mmol/L]、CRP[(2.01±1.79)mg/L比(3.14±2.92)mg/L]水平显著升高(P0.05);(2)LEAD组及NLEAD组的SDNN、SDANN、VLF及血浆脂联素含量均显著低于正常对照组(P0.05),与NLEAD组比较,LEAD组HRV指标除rMSSD外显著下降(P0.05);(3)糖尿病下肢病变的发生与病程、SBP、2hPG、HbA1c、LDL-C、Fg、CRP呈正相关(r=0.760~0.331,P均0.05),而与脂联素及心率变异指数呈负相关(r=-0.597~-0.317,P均0.05);(4)多元Logistic回归分析显示,糖尿病的病程、SBP、HbA1c、LDL-C、CRP、老年2型糖尿病下肢动脉病变的独立危险因素(OR=2.932~14.404,P0.05)。结论:(1)糖尿病的病程、SBP、HbA1c、LDL-C、CRP、脂联素、HRV与老年2型糖尿病患者下肢动脉病变相关;(2)HRV降低是老年2型糖尿病患者下肢动脉病变的独立危险因素。     

Characteristics of children with type 1 diabetes and persistent suboptimal glycemic control

Objective: This study aims to determine the relationship between the duration of persistent poor glycemic control in type 1 diabetes mellitus (T1DM) children and the likelihood of subsequent improvement.Methods: A retrospective cohort study was conducted on T1DM patients aged 6-18 years, followed for at least six visits at Children’s National Medical Center (Washington, DC) with at least one hemoglobin A1c (HbA1c) ≥10% after the first year since the initial visit (n=151). Medical records of patients with subsequently improved glycemic control were reviewed (n=39).Results: Patients aged 12-18 years, females, and Medicaid patients were twice as likely to be in persistently poor control as patients aged 6-11 years, males, and privately insured patients, respectively. Each additional visit with HbA1c ≥10% and one percentage point increase in the mean HbA1c reduced the likelihood of subsequent improvement by 20% and 50%, respectively. Of the 39 patients with improved control, only 5 (13%) sustained their improvement for ≥2 years. Multiple contributing factors for improved control were identified, but no one factor explained improved control in >25% of patients.Conclusion This study suggests that the longer the duration of poor control, the more difficult it is to reverse the underlying factors of poor diabetes management. Strategies to improve regular clinic attendance along with reinforcement of changes which resulted in improved control are critical. Adolescents, females, and Medicaid patients in particular should be targeted for sustained intervention. Conflict of interest:None declared.     

1型糖尿病起病过程的临床异质性分析

目的 了解1型糖尿病起病过程的临床异质性.方法 回顾性分析自1999年1月至2009年12月广州中山大学附属第一医院内分泌科205例新诊断1型糖尿病患者的临床资料.根据症状出现至就诊时间,将患者分为暴发性1型糖尿病（FT1DM）、急性起病及缓慢起病的1型糖尿病（出现症状至就诊时间分别≤或＞3个月）,比较3组患者临床特点及实验室检查资料.血清谷氨酸脱羧酶抗体（GADA）、胰岛细胞自身抗体（ICA）、胰岛素自身抗体（IAA）均为定性检测,GADA采用酶联免疫吸附法（ELISA）,ICA、IAA及血清C肽检测采用放射免疫法.计量资料采用单因素方差分析或两个独立样本的t检验,计数资料采用多变量卡方检验及Fisher精确概率法进行统计分析.结果 FT1DM、急性起病及缓慢起病的1型糖尿病分别占8.8%、66.8%及24.4%.3组中FT1DM患者血糖升高更明显[分别为（31±12）、（25±10）、（24±8）mmol/L,F=4.462,P＜0.05],而糖化血红蛋白略高于正常[分别为（6.8±1.1）%、（12.3±2.4）%、（13.9±2.7）%,F=54.661,P＜0.05],酮症酸中毒更常见（分别为93.8%、45.3%、8.0%,F=44.943,P=0.000）,合并低钠血症、高钾血症、酸中毒、肝肾功能受损更严重,合并妊娠的比例更高（分别为22.2%、0、0,X2=20.982,P=0.000）.缓慢起病的1型糖尿病患者起病年龄及体质指数较另两组大,而体质量下降更明显,负荷后C肽水平明显高于另外两组[分别为（0.40±0.36）、（0.10±0.13）、（0.34±0.26）nmol/L,F=8.752,P＜0.05].儿童及青少年在急性起病的1型糖尿病中所占比例更高,其临床表型与成人相似.结论3组患者起病过程的临床异质性十分明显,提示1型糖尿病可能存在不同的疾病触发机制.     

Swedish guidelines for type 1 diabetes and pregnancy outcomes: A nationwide descriptive study of consensus and adherence

AimsType 1 diabetes (DM1) during pregnancy and labor is associated with an increased risk of maternal and fetal complications. Evidence-based care is therefore provided in accordance with guidelines.In this study, we aimed to compare all the Swedish guidelines for DM1 during pregnancy and labor in terms of the variables emphasized in the national guidelines from the US and from England and Wales. The second aim was to measure adherence to local guidelines at the four hospitals in Stockholm that cared for pregnant women with DM1 during 2016 and to describe the pregnancy and labor outcomes.MethodsAll the Swedish guidelines for DM1 during pregnancy and labor were reviewed on 31 variables. The medical records of 114 women were reviewed according to whether ≥70% of 22 variables in the guidelines were followed.ResultsNo consensus was found in the Swedish guidelines for any of the 31 variables. Some guidelines were contradictory. The pregnancy guidelines were followed in 17.5% of the medical records, 18.4% followed the labor guidelines, and 5.3% followed both guidelines. The onset of labor, mode of delivery and HbA1c in the third trimester varied significantly, depending on the adherence to guidelines.ConclusionsThe Swedish guidelines for DM1 during pregnancy and labor lack both consensus and adherence. A national guideline on DM1 during pregnancy and childbirth with high adherence could improve care for pregnant Swedish women with DM1 and their fetuses.