Outcomes of type 1 diabetes mellitus in pregnancy; effect of excessive gestational weight gain and hyperglycaemia on fetal growth

AimsTo study pregnancy outcomes in patients with type 1 diabetes mellitus (T1DM) and the factors associated with poor outcomes.MethodsA retrospective study of 110 patients with T2DM who attended our diabetes in pregnancy clinic at the Women's Wellness and Research centre, Doha, between March 2015 and December 2016 and 1419 normoglycaemic controls.ResultsThere was no difference in age, weight, and BMI between the two groups. The incidence of macrosomia, shoulder dystocia and stillbirth were similar in the two groups while that of pre-term labour, pre-eclampsia, Caesarean section (CS), large for gestational age (LGA), neonatal ICU (NICU) admission and neonatal hypoglycaemia were significantly higher in the T1DM than in the control group. From a multivariate regression analysis, excessive gestational weight gain was associated with increased risk of LGA (OR 4.53; 95% CI [1.42–14.25]). Last trimester HBA1c was associated with increased risk for macrosomia [OR 2.46, 95% CI [1.03–5.86)]; LGA [ OR 3.25, 95% CI [1.65–6.40)]; increased risk for C-section (OR 1.96, 95% CI [1.12–3.45]), and increased risk of NICU admission (OR 2.46, 95% CI [1.04–5.86]). The changes in HBA1C between the first and last trimester HBA1c was associated with a reduction in the risk of LGA [OR 0.46, 95% CI [(0.28–0.75)]ConclusionT1DM in pregnancy is associated with adverse pregnancy outcomes compared to the general population. Reducing gestational weight gain and improving glycaemic control might improve pregnancy outcomes.     

Weight gain in type 2 diabetes mellitus

OBJECTIVE: To investigate the potential causes of weight gain using insulin and combination therapy in type 2 diabetes. DESIGN AND METHODS: This was an open-label prospective study of 6-month duration. Randomization was performed to insulin monotherapy, insulin and pioglitazone 30 mg daily, or insulin and metformin up to 2000 mg daily. Fifty-seven subjects with poorly controlled type 2 diabetes were enrolled. The goal was to achieve a normal haemoglobin A1c (HbA1c) (<5.6%). Weight, resting energy expenditure (REE), reported energy intake and total energy expenditure, HbA1c, glycosuria, plasma leptin, ghrelin and adiponectin levels, and body fat were measured. RESULTS: A total of 49 subjects completed the study. At baseline, weight was 89.4 +/- 22.9 kg and HbA1c was 11.1 +/- 1.5%. Weight increased by 7.46, 7.60 and 7.12 kg in the monotherapy, metformin and pioglitazone groups, respectively [p = 0.98 between and <0.0001 within the groups by repeated measures-analysis of variance (RM-anova)]. HbA1c dropped to 7.8 +/- 0.9% in the monotherapy arm, 7.6 +/- 1.0% in the metformin arm and 7.2 +/- 1.2% in the pioglitazone arm. Reported energy intake decreased. Glycosuria decreased but was not correlated with weight gain, while HbA1c changes were correlated with weight gain. REE per lean mass decreased (p = 0.04 by RM-anova). The subcutaneous fat areas in the insulin monotherapy and pioglitazone arms showed increases (p = 0.02 and 0.004 respectively). CONCLUSIONS: Weight gain was probably not due to an increase in food intake, while REE per lean body mass decreased, suggesting a role for increased efficiency in fuel usage due to improved glycaemic control. A drop in glycosuria probably also contributed to weight gain. In the monotherapy and pioglitazone arms, the subcutaneous fat areas increased.     

Non‐severe hypoglycaemia is associated with weight gain in patients with type 1 diabetes: Results from the Diabetes Control and Complication Trial

It is unclear whether the frequent non‐severe episodes of hypoglycaemia observed during intensive glucose control in individuals with type 1 diabetes (T1D) are associated with subsequent weight gain. We analysed the association between non‐severe hypoglycaemia and weight gain in 1441 Diabetes Control and Complication Trial (DCCT) participants. Non‐severe hypoglycaemia was assessed by hypo‐score (ie, number of blood glucose values <70 mg/dL divided by the total number of measurements during the DCCT quarterly visits). Significant associations were observed between the hypo‐score and annual and total weight gain. The annual weight gain by hypo‐score tertiles was 0.8 ± 1.2 (T1), 1.3 ± 1.5 (T2) and 1.4 ± 1.3 kg/y (T3), P < .001 for T2 and T3 vs T1, and for T3 vs T2. The odds ratio for a weight gain of 1.8 kg/y was 2.14 (95% CI, 1.56‐2.93) for T2, and 2.53 (95%CI, 1.85‐3.45) for T3 vs T1. These differences in weight gain and in risk of weight gain remained significant after adjustment for sex, age, duration of diabetes, HbA1c at baseline and treatment arms. In conclusion, our analysis shows a significant association between non‐severe hypoglycaemia and weight gain in individuals with T1D from the DCCT.     

Quantitative relationship between body weight gain in adulthood and incident type 2 diabetes: a meta‐analysis

This meta‐analysis quantified the risk of type 2 diabetes mellitus (T2DM) preceded by body weight (BW) gain in the general population. Systematic literature searches retrieved 15 eligible studies. The BW gain was divided into early weight‐gain, which was defined as BW gain from early adulthood (18–24 years of age) to cohort entry (≥25 years of age), and late weight‐gain, which was defined as BW gain from cohort entry. The pooled relative risk (RR; 95% confidence interval [CI]) of T2DM for an increment of BW gain standardized into a 5‐kg m^?2 increment in the body mass index (BMI) was 3.07 (2.49–2.79) for early weight‐gain and 2.12 (1.74–2.58) for late weight‐gain. When limiting analysis to studies that concurrently examined T2DM risk for current BMI (defined in both groups as BMI at cohort entry), a larger magnitude of T2DM risk was revealed for early weight‐gain compared with current BMI (RR [95% CI], 3.38 [2.20–5.18] vs. 2.39 [1.58–3.62]), while there was little difference between late weight‐gain (RR [95% CI], 2.21 [1.91–2.56]) and current BMI (RR [95% CI], 2.47 [1.97–3.30]). The meta‐analysis suggested that BW gain was a quantifiable predictor of T2DM, as well as current obesity in adults. Particularly, BW gain in early rather than middle‐to‐late adulthood played an important role in developing T2DM.     

Glycaemic control without weight gain in insulin requiring type 2 diabetes: 1-year results of the GAME regimen

INTRODUCTION: Weight gain appears to be unavoidable in patients with type 2 diabetes who are switched from oral agents to insulin therapy. Peripheral hyperinsulinism induced by the use of long-acting insulin may be the key to explain this adverse effect. AIM: The aim of this study was to investigate whether a regimen free of long-acting insulin can provide long-term glycaemic control without causing weight gain. PATIENTS AND METHODS: This is an uncontrolled, 1-year study comprising 58 patients with type 2 diabetes and secondary failure, age 30-75 years, BMI 25-35 kg/m(2), HbA1c > 7.5% and fasting C-peptide level > 0.3 mmol/l. All patients were treated with the GAME regimen, a combination of glimepiride administered at 20:00 hours for nocturnal glycaemic control, insulin aspart three times daily for meal-related glucose control and metformin. RESULTS: Seventy-one per cent of the patients were considered evaluable. HbA1c decreased from 10.0 +/- 0.3 to 7.4 +/- 0.1% (p < 0.001). Fifty-nine per cent reached HbA1c levels 相似文献   

1型糖尿病的免疫治疗

1型糖尿病（T1DM）是一种自身免疫性疾病,人们希望基于发病机制进行免疫干预治疗可以达到预防和逆转 T1DM的目的。近30余年,免疫干预临床试验逐渐开展,包括免疫调节药物、调节性T细胞、干细胞治疗和胰岛移植 等。尽管这些试验通过抑制自身免疫应答或胰岛B细胞替代,可以延缓胰岛B细胞功能的衰退或短期内脱离胰岛素 治疗,但仍有各自的局限性。文章将结合最新的临床试验数据对免疫干预治疗T1DM的研究进展进行总结和展望。     

Insulin-associated weight gain in diabetes--causes, effects and coping strategies

Insulin therapy or intensification of insulin therapy commonly results in weight gain in both type 1 and type 2 diabetes. This weight gain can be excessive, adversely affecting cardiovascular risk profile. The spectre of weight gain can increase diabetic morbidity and mortality when it acts as a psychological barrier to the initiation or intensification of insulin, or affects adherence with prescribed regimens. Insulin-associated weight gain may result from a reduction of blood glucose to levels below the renal threshold without a compensatory reduction in calorie intake, a defensive or unconscious increase in calorie intake caused by the fear or experience of hypoglycaemia, or the 'unphysiological' pharmacokinetic and metabolic profiles that follow subcutaneous administration. There is, however, scope for limiting insulin-associated weight gain. Strategies include limiting dose by increasing insulin sensitivity through diet and exercise or by using adjunctive anorectic or insulin-sparing pharmacotherapies such as pramlintide or metformin. Insulin replacement regimens that attempt to mimic physiological norms should also enable insulin to be dosed with maximum efficiency. The novel acylated analogue, insulin detemir, appears to lack the usual propensity for causing weight gain. Elucidation of the pharmacological mechanisms underlying this property might help clarify the mechanisms linking insulin with weight regulation.     

Insulin-induced weight gain and cardiovascular events in patients with type 2 diabetes. A report from the DIGAMI 2 study

Aim:  We investigated whether insulin treatment-induced weight gain was accompanied by increased cardiovascular (CV) mortality and morbidity in the second Diabetes Insulin Glucose in Acute Myocardial Infarction (DIGAMI 2) study.
Methods:  We studied the 865 patients who survived during 12 months without any change in their glucose-lowering (GL) therapy. They were divided into four subgroups according to GL treatment: group I, no pharmacological GL treatment (n = 99); group II, oral hypoglycaemic agents (n = 250); group III, new insulin treatment (n = 245) and group IV, insulin before inclusion continued during the first year of follow up (n = 271).
Results:  Patients who started on insulin (group III) experienced an average body weight increase of 2.3 (1.5–3.2) kg during the first year of treatment, whereas weight remained unchanged in groups I, II and IV. The incidence of non-fatal reinfarction was higher in group III compared with the other groups (hazard ratio (HR) = 2.5, p   = 0.011) and CV mortality was higher in group IV (HR = 2.4, p   = 0.003). When the subjects were grouped in quartiles according to maximal body weight increase, those in the lowest quartile experienced the highest CV mortality. Each kilogram increase in weight reduced the risk for CV death with 6%. The incidence of reinfarction did not differ between quartiles.
Conclusions:  Initiation of insulin treatment after myocardial infarction was associated with a significant increase in weight and incidence of reinfarction. The increase in weight did, however, not explain the increased rate of reinfarction.     

Prevention of weight gain in type 2 diabetes requiring insulin treatment

Background: Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds.
Aim: To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin.
Methods: In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1–2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control.
Results: Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 ± 0.3 mg/day (mean ± standard error of the mean), and a total daily insulin dose of 24.1 ± 2.6 IU. Fasting glucose levels decreased from 12.7 ± 0.6 mmol/l to 8.1 ± 0.3 mmol/l (p  <  0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 ± 0.4 to 7.7 ± 0.2% (p  <  0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 ± 3.6 kg vs. 85.7 ± 3.3 kg, p = 0.99).
Conclusion: The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.     

Insulin oedema in newly diagnosed type 1 diabetes mellitus

Despite the essential role of insulin in the management of patients with insulin deficiency, insulin use can lead to adverse effects such as hypoglycaemia and weight gain. Rarely, crucial fluid retention can occur with insulin therapy, resulting in an oedematous condition. Peripheral or generalised oedema is an extremely rare complication of insulin therapy in the absence of heart, liver or renal involvement. It has been reported in newly diagnosed type 1 diabetes, in poorly controlled type 2 diabetes following the initiation of insulin therapy, and in underweight patients on large doses of insulin. The oedema occurs shortly after the initiation of intensive insulin therapy. We describe two adolescent girls with newly diagnosed type 1 diabetes, who presented with oedema of the lower extremities approximately one week after the initiation of insulin treatment; other causes of oedema were excluded. Spontaneous recovery was observed in both patients.     

The association between weight gain at different stages of pregnancy and risk of gestational diabetes mellitus

Aims/IntroductionWomen with excessive gestational weight gain (GWG) are at a higher risk for complications during pregnancy, such as preeclampsia. However, the association between excessive GWG and gestational diabetes mellitus (GDM) remains unclear.Materials and MethodsWe retrospectively reviewed 8,352 women from our obstetric database with singleton pregnancies who gave birth after 28 completed weeks of gestation between January 1, 2012, and December 31, 2016, excluding pregnancies complicated by fetal anomalies, fetal death, and overt diabetes. Diagnosis of GDM was based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups. We used two classification methods to define excessive GWG: a weight gain above the 90th percentile of the population, or exceeding the upper range recommended by the Institute of Medicine, stratified by pre‐pregnancy body mass index. Statistical analysis was performed using multiple logistic regression to determine the association between excessive GWG and the risk of GDM.ResultsOverall, 1,129 women (13.5%) were diagnosed with GDM. There was no difference in GWG between women with and without GDM in the first trimester and before GDM screening. Women with GDM had significantly less GWG in the second trimester, after GDM screening, and throughout the whole gestation than women without GDM. No correlation was found between excessive GWG in the first and second trimesters, before GDM screening, and the later development of GDM.ConclusionsOur results indicate that excessive GWG prior to GDM screening is not associated with an increased risk of GDM.     

Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis

Aims

Higher doses of the glucagon-like peptide-1 agonist semaglutide and, more recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money.

Materials and Methods

We calculated the cost needed to treat to achieve a 1% reduction in body weight using high-dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT-1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022.

Results

Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%-19.3%) compared with 12.4% (95% CI: 11.5%-13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908-$1075) compared with $1845 (95% CI: $1707-$1989) with semaglutide. Scenario analysis confirmed these findings.

Conclusions

Tirzepatide provides better value for money than semaglutide for weight reduction.     

Comparison of alogliptin and glipizide for composite endpoint of glycated haemoglobin reduction,no hypoglycaemia and no weight gain in type 2 diabetes mellitus

This was a post hoc analysis of a 2‐year, double‐blind study of 2639 patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy, which assessed achievement of a composite endpoint of sustained glycated haemoglobin (HbA1c) reduction (≤7.0% at week 104 or ≥0.5% decrease from baseline) with no weight gain and no hypoglycaemic events with alogliptin 12.5 and 25 mg daily or glipizide (≤20 mg daily), each added to metformin. With an HbA1c target of ≤7.0%, 24.2 and 26.9% of patients treated with alogliptin 12.5 and 25 mg, respectively, achieved the composite endpoint versus 10.7% of patients treated with glipizide (both p < 0.001). With a criterion of ≥0.5% decrease in HbA1c, the composite endpoint was reached in 22.5, 25.2 and 10.4% of patients treated with alogliptin 12.5 mg, alogliptin 25 mg and glipizide, respectively. Odds ratios for achieving the composite endpoint favoured alogliptin in the primary analysis set and in all subgroups of patients. Patients with T2DM failing metformin monotherapy were more likely to achieve sustained glycaemic control with no hypoglycaemia or weight gain at 2 years with alogliptin than with glipizide.     

Less frequent body weight gain in elderly type 2 diabetic patients treated with glimepiride

Background:   The purpose of the present paper was to study the effect of a new sulfonylurea, glimepiride, which has an extra-pancreatic action that improves insulin resistance, on glycemic control and body weight gain in elderly patients with type 2 diabetes mellitus (DM).
Methods:   Thirty-seven type 2 diabetic patients being treated with either gliclazide or glibenclamide were switched to glimepiride for 6 months and clinical parameters were compared between elderly (≥ 65 years old, n  = 9) and non-elderly (< 65 years old, n  = 28) patients.
Results:   There was no significant difference between the two groups in baseline characteristics, or in changes in fasting plasma glucose (FPG) and HbA1c. For body weight change, however, none of the elderly patients (0/9) exhibited an increase, but 9 of 28 (32%) non-elderly subjects showed body weight gain ( P  < 0.05).
Conclusions:   Body weight gain with glimepiride treatment is less frequent in elderly patients with type 2 DM than in non-elderly patients with the disease. These data together with the recent increase in obese elderly patients with diabetes suggest that glimepiride is recommended for treatment of type 2 diabetes in this age group.     

The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis

Aim: The objective of this systematic review and meta‐analysis was to assess the effect of pramlintide on glycemic control, weight and incidence of nausea and hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) and in obese patients without diabetes (OBP). Methods: Eight randomized, clinical trials were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. Results: In four T2DM studies (N = 930,duration of studies 16–52weeks,120–150mcg/dose BID–TID), all patients received insulin therapy. In four obesity studies (N = 686,duration of studies 6–24weeks,120–360mcg/dose BID–TID), equivalent volumes of placebo were administered before major meals. Pramlintide significantly reduced haemoglobin A1c (HbA1c) (?0.33% [95% CI ?0.51, ?0.14], p = 0.004) and weight (?2.57 kg, [95% CI ?3.44, ?1.70], p < 0.00001) versus the control group. More patients in the control group reported hypoglycaemia of any severity versus the pramlintide group (risk ratio 0.84 [95% CI 0.69, 10.3], p = 0.09). In OBP, pramlintide caused a reduction in weight (?2.27 kg [95% CI ?2.88, ?1.66], p < 0.00001). When event data from both populations were combined, patients randomized to pramlintide were 1.8 times more likely to report nausea of any severity versus control (p = 0.0005). Conclusions: Pramlintide was associated with a small reduction in HbA1c, and a modest reduction in weight in patients with T2DM or OBP. There was increased incidence of nausea but not hypoglycaemia at any time during therapy. Studies about the long‐term effect of pramlintide on diabetes‐ and cardiovascular‐related complications and cost‐effectiveness analyses are needed.     

Low insulin-like growth factor-II levels predict weight gain in normal weight subjects with type 2 diabetes

Purpose

Insulin-like growth factor (IGF)-I and IGF-II are important in the regulation of metabolism and growth. We previously reported in normoglycemic individuals of normal weight that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of type 2 diabetes.

Methods

In 224 subjects with type 2 diabetes we assessed the association between baseline IGF-II levels and risk of weight gain (>2.0 kg) at the 5-year follow-up.

Results

At follow-up, 90 participants (40.2%) gained more than 2.0 kg in body weight. For subjects (body mass index <26) at baseline, mean IGF-II levels were significantly lower in those who gained more than 2 kg in weight than in subjects of stable weight, 454 ng/mL (95% confidence interval 349-559) versus 620 ng/mL (534-705) (F = 7.4, P = .01). For this subgroup low circulating IGF-II at baseline strongly correlated with weight gain (Spearman rho = −0.52, P <.001). With increasing weight, the relationship no longer prevailed. Logistic regression showed that for body mass index less than 26, individuals at baseline for each 100 ng/mL increase in baseline IGF-II there was a 47% decreased risk of gaining 2.0 kg or more in weight. Adjustment for treatment group did not materially alter this relationship. There was no difference in baseline IGF-II by treatment group. There was no difference between the group with weight gain and the group with stable weight in those who additionally received insulin or sulfonylurea treatment in the 5 years between the baseline visit and the follow-up.

Conclusions

In subjects of normal weight with type 2 diabetes, baseline IGF-II concentration is inversely related to future weight gain, independent of treatment effect, strengthening the putative role for IGF-II in regulating fat mass. We propose that IGF-II measurement has potential utility in this group for targeting such individuals for early intervention.     

A cohort study of reproductive risk factors,weight and weight change and the development of diabetes mellitus

Aims:  Reproductive factors (parity, miscarriages, terminations), oral contraceptive use, hormone replacement therapy, body weight at first pregnancy and weight gain following pregnancy may be associated with a long-term risk of diabetes. The aim of this study is to investigate the independent risks of reproductive factors and body weight for diabetes in later life.
Methods:  This is a retrospective cohort study of 1257 parous women who had a first pregnancy between 1951 and 1970. Reproductive history, weight and height were measured at the time of first pregnancy, then assessed by questionnaire in 1997 for all women. A clinical examination and an analysis of blood samples were undertaken for 992 women. The main outcome was incidence of diabetes based on medical history, medication and random glucose measurement.
Results:  Sixty of the 1257 (4.8%) women developed diabetes. Body mass index at index pregnancy and after 28–48 years follow-up were both significantly associated with risk of diabetes, this increased with greater weight gain. There was a non-significant increased risk of diabetes associated with stillbirths and miscarriages after age and BMI adjustment.
Conclusions:  In parous women, higher BMI at index pregnancy, weight gain during follow-up and BMI in later life strongly predict diabetes risk.     

Benefits of moderate weight loss in patients with type 2 diabetes

Weight loss is a primary goal of therapy in overweight patients with type 2 diabetes. This review examines whether positive patient outcomes are observed even after relatively small amounts of weight loss, that is, weight loss being more easily attainable in practice. Clinical studies demonstrate that therapeutic benefit rises with increasing weight loss, but that losses as low as 0.45–4 kg (1–9 lb) have positive effects on metabolic control, cardiovascular risk factors and mortality rates. Even the intention to lose weight, without significant success, can improve outcomes in patients with diabetes, presumably because of the healthy behaviours associated with the attempt. The current data support a continued focus on weight loss, including moderate weight loss, as a key component of good care for overweight patients with type 2 diabetes.