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Oral anti-diabetic agents for women with established diabetes/impaired glucose tolerance or previous gestational diabetes planning pregnancy, or pregnant women with pre-existing diabetes.
Tieu, J, Coat, S, Hague, W, Middleton, P, Shepherd, E
The Cochrane database of systematic reviews. 2017;(10):CD007724
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Abstract
BACKGROUND While most guidance recommends the use of insulin in women whose pregnancies are affected by pre-existing diabetes, oral anti-diabetic agents may be more acceptable to women. The effects of these oral anti-diabetic agents on maternal and infant health outcomes need to be established in pregnant women with pre-existing diabetes or impaired glucose tolerance, as well as in women with previous gestational diabetes mellitus preconceptionally or during a subsequent pregnancy. This review is an update of a review that was first published in 2010. OBJECTIVES To investigate the effects of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who are planning a pregnancy, or pregnant women with pre-existing diabetes, on maternal and infant health. The use of oral anti-diabetic agents for the management of gestational diabetes in a current pregnancy is evaluated in a separate Cochrane Review. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2016) and reference lists of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who were planning a pregnancy, or pregnant women with pre-existing diabetes. Cluster-RCTs were eligible for inclusion, but none were identified. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included RCTs. Review authors checked the data for accuracy, and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS We identified six RCTs (707 women), eligible for inclusion in this updated review, however, three RCTs had mixed populations (that is, they included pregnant women with gestational diabetes) and did not report data separately for the relevant subset of women for this review. Therefore we have only included outcome data from three RCTs; data were available for 241 women and their infants. The three RCTs all compared an oral anti-diabetic agent (metformin) with insulin. The women in the RCTs that contributed data had type 2 diabetes diagnosed before or during their pregnancy. Overall, the RCTs were judged to be at varying risk of bias. We assessed the quality of the evidence for selected important outcomes using GRADE; the evidence was low- or very low-quality, due to downgrading because of design limitations (risk of bias) and imprecise effect estimates (for many outcomes only one or two RCTs contributed data).For our primary outcomes there was no clear difference between metformin and insulin groups for pre-eclampsia (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.33 to 1.20; RCTs = 2; participants = 227; very low-quality evidence) although in one RCT women receiving metformin were less likely to have pregnancy-induced hypertension (RR 0.58, 95% CI 0.37 to 0.91; RCTs = 1; participants = 206; low-quality evidence). Women receiving metformin were less likely to have a caesarean section compared with those receiving insulin (RR 0.73, 95% CI 0.61 to 0.88; RCTs = 3; participants = 241; low-quality evidence). In one RCT there was no clear difference between groups for large-for-gestational-age infants (RR 1.12, 95% CI 0.73 to 1.72; RCTs = 1; participants = 206; very low-quality evidence). There were no perinatal deaths in two RCTs (very low-quality evidence). Neonatal mortality or morbidity composite outcome and childhood/adulthood neurosensory disability were not reported.For other secondary outcomes we assessed using GRADE, there were no clear differences between metformin and insulin groups for induction of labour (RR 1.42, 95% CI 0.62 to 3.28; RCTs = 2; participants = 35; very low-quality evidence), though infant hypoglycaemia was reduced in the metformin group (RR 0.34, 95% CI 0.18 to 0.62; RCTs = 3; infants = 241; very low-quality evidence). Perineal trauma, maternal postnatal depression and postnatal weight retention, and childhood/adulthood adiposity and diabetes were not reported. AUTHORS' CONCLUSIONS There are insufficient RCT data to evaluate the use of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who are planning a pregnancy, or in pregnant women with pre-existing diabetes. Low to very low-quality evidence suggests possible reductions in pregnancy-induced hypertension, caesarean section birth and neonatal hypoglycaemia with metformin compared with insulin for women with type 2 diabetes diagnosed before or during their pregnancy, and no clear differences in pre-eclampsia, induction of labour and babies that are large-for-gestational age. Further high-quality RCTs that compare any combination of oral anti-diabetic agent, insulin and dietary and lifestyle advice for these women are needed. Future RCTs could be powered to evaluate effects on short- and long-term clinical outcomes; such RCTs could attempt to collect and report on the standard outcomes suggested in this review. We have identified three ongoing studies and four are awaiting classification. We will consider these when this review is updated.
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The impact of triglycerides on glucose tolerance: Lipotoxicity revisited.
Seghieri, M, Tricò, D, Natali, A
Diabetes & metabolism. 2017;(4):314-322
Abstract
Elevated plasma triglycerides (TGs) are early key features of conditions associated with a dysregulation in glucose metabolism and may predict the development of type 2 diabetes (T2D) over time. Although the acute ingestion of lipid, either mixed with or shortly before the meal, is neutral or slightly beneficial on glucose tolerance, a short-term increase in plasma TGs induced by either an i.v. lipid infusion or a high-fat diet produces a deterioration of glucose control. Accordingly, chronic lowering of plasma TGs by fibrates improves glucose homeostasis and may also prevent T2D. The chronic effects of the elevation of dietary lipid intake are less clear, particularly in humans, being the quality of fat probably more important than total fat intake. Although on the bases of the available experimental and clinical evidence it cannot be easily disentangled, with respect to elevated non-esterified fatty acids (NEFA) the relative contribution of elevated TGs to glucose homeostasis disregulation seems to be greater and also more plausible. In conclusion, although the association between elevated plasma TGs and impaired glucose tolerance is commonly considered not causative or merely a consequence of NEFA-mediated lipotoxicity, the available data suggest that TGs per se may directly contribute to disorders of glucose metabolism.
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Chronic fructose substitution for glucose or sucrose in food or beverages has little effect on fasting blood glucose, insulin, or triglycerides: a systematic review and meta-analysis.
Evans, RA, Frese, M, Romero, J, Cunningham, JH, Mills, KE
The American journal of clinical nutrition. 2017;(2):519-529
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Abstract
Background: Conflicting evidence exists on the role of long-term fructose consumption on health. No systematic review has addressed the effect of isoenergetic fructose replacement of other sugars and its effect on glycated hemoglobin (HbA1c), fasting blood glucose, insulin, and triglycerides.Objective: The objective of this study was to review the evidence for a reduction in fasting glycemic and insulinemic markers after chronic, isoenergetic replacement of glucose or sucrose in foods or beverages by fructose. The target populations were persons without diabetes, those with impaired glucose tolerance, and those with type 2 diabetes.Design: We searched the Cochrane Library, MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov The date of the last search was 26 April 2016. We included randomized controlled trials of isoenergetic replacement of glucose, sucrose, or both by fructose in adults or children with or without diabetes of ≥2 wk duration that measured fasting blood glucose. The main outcomes analyzed were fasting blood glucose and insulin as well as fasting triglycerides, blood lipoproteins, HbA1c, and body weight.Results: We included 14 comparison arms from 11 trials, including 277 patients. The studies varied in length from 2 to 10 wk (mean: 28 d) and included doses of fructose between 40 and 150 g/d (mean: 68 g/d). Fructose substitution in some subgroups resulted in significantly but only slightly lowered fasting blood glucose (-0.14 mmol/L; 95% CI: -0.24, -0.036 mmol/L), HbA1c [-10 g/L (95% CI: -12.90, -7.10 g/L; impaired glucose tolerance) and -6 g/L (95% CI: -8.47, -3.53 g/L; normoglycemia)], triglycerides (-0.08 mmol/L; 95% CI: -0.14, -0.02 mmol/L), and body weight (-1.40 kg; 95% CI: -2.07, -0.74 kg). There was no effect on fasting blood insulin or blood lipids.Conclusions: The evidence suggests that the substitution of fructose for glucose or sucrose in food or beverages may be of benefit to individuals, particularly those with impaired glucose tolerance or type 2 diabetes. However, additional high-quality studies in these populations are required.
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Effect of lifestyle interventions on glucose regulation among adults without impaired glucose tolerance or diabetes: A systematic review and meta-analysis.
Zhang, X, Imperatore, G, Thomas, W, Cheng, YJ, Lobelo, F, Norris, K, Devlin, HM, Ali, MK, Gruss, S, Bardenheier, B, et al
Diabetes research and clinical practice. 2017;:149-164
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Abstract
This study systematically assessed the effectiveness of lifestyle interventions on glycemic indicators among adults (⩾18years) without IGT or diabetes. Randomized controlled trials using physical activity (PA), diet (D), or their combined strategies (PA+D) with follow-up ⩾12months were systematically searched from multiple electronic-databases between inception and May 4, 2016. Outcome measures included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin (FI), homeostasis model assessment-estimated insulin resistance (HOMA-IR), and bodyweight. Included studies were divided into low-range (FPG <5.5mmol/L or HbA1c <5.5%) and high-range (FPG ⩾5.5mmol/L or HbA1c ⩾5.5%) groups according to baseline glycemic levels. Seventy-nine studies met inclusion criteria. Random-effect models demonstrated that compared with usual care, lifestyle interventions achieved significant reductions in FPG (-0.14mmol/L [95%CI, -0.19, -0.10]), HbA1c (-0.06% [-0.09, -0.03]), FI (%change: -15.18% [-20.01, -10.35]), HOMA-IR (%change: -22.82% [-29.14, -16.51]), and bodyweight (%change: -3.99% [-4.69, -3.29]). The same effect sizes in FPG reduction (0.07) appeared among both low-range and high-range groups. Similar effects were observed among all groups regardless of lengths of follow-up. D and PA+D interventions had larger effects on glucose reduction than PA alone. Lifestyle interventions significantly improved FPG, HbA1c, FI, HOMA-IR, and bodyweight among adults without IGT or diabetes, and might reduce progression of hyperglycemia to type 2 diabetes mellitus.
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Adult Consequences of Extremely Preterm Birth: Cardiovascular and Metabolic Diseases Risk Factors, Mechanisms, and Prevention Avenues.
Nuyt, AM, Lavoie, JC, Mohamed, I, Paquette, K, Luu, TM
Clinics in perinatology. 2017;(2):315-332
Abstract
Extremely preterm babies are exposed to various sources of injury during critical stages of development. The extremely preterm infant faces premature transition to ex utero physiology and undergoes adaptive mechanisms that may be deleterious in the long term because of permanent alterations in organ structure and function. Perinatal events can also directly cause structural injury. These disturbances induce morphologic and functional changes in their organ systems that might heighten their risks for later adult chronic diseases. This review examines the pathophysiology of programming of long-term health and diseases after preterm birth and associated perinatal risk factors.
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Definitions (and Current Controversies) of Diabetes and Prediabetes.
Buysschaert, M, Medina, JL, Buysschaert, B, Bergman, M
Current diabetes reviews. 2016;(1):8-13
Abstract
Diagnosis of type 2 diabetes and prediabetes is mandatory. Chronic hyperglycemia in diabetes is associated with long-term micro- and macrovascular as well as with neurological complications. Prediabetes predisposes patients to develop diabetes and macrovascular disease. Diagnosis of diabetes is established on (at least) one of the following criteria: a fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/l), a casual plasma glucose ≥ 200 mg/dl (11.1 mmol/l) in the presence of symptoms, a 2-h plasma glucose during the 75-g oral glucose tolerance test (OGTT) ≥ 200 mg/dl (11.1 mmol/l) and/or an HbA1c ≥ 6.5%. Prediabetes is defined by the Position Statement of the American Diabetes Association as a fasting plasma glucose between 100 and 125 mg/dl (5.6 - 6.9 mmol/l) [a condition called Impaired Fasting Glucose] and/or by a 2-h plasma glucose during OGTT 140 - 199 mg/dl (7.8 - 11.0 mmol) [Impaired Glucose Tolerance] and/or a HbA1c level 5.7 - 6.4%, with however some potential discordance between tests. The threshold of fasting plasma glucose defining Impaired Fasting Glucose as well as the adequacy of HbA1c as a correct diagnostic tool for prediabetes is still debated.
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Postpartum Lifestyle Interventions to Prevent Type 2 Diabetes Among Women with History of Gestational Diabetes: A Systematic Review of Randomized Clinical Trials.
Guo, J, Chen, JL, Whittemore, R, Whitaker, E
Journal of women's health (2002). 2016;(1):38-49
Abstract
Women with a history of gestational diabetes mellitus (GDM) are at a higher risk of developing type 2 diabetes. Several postpartum lifestyle intervention studies have been conducted for this high-risk group; however, the randomized clinical trials have not been evaluated systematically. Thus, the aim of this article is to evaluate the outcomes of clinical trials that focus on diabetes prevention among women with DGM. This systematic review utilized Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Chinese and US databases were searched. Randomized controlled trials of postpartum lifestyle interventions to prevent type 2 diabetes in women with prior GDM were reviewed. Outcomes included in this review are type 2 diabetes incidences, insulin insistence, and weight-related measures. The effect size of these outcomes in each study was computed. Data on intervention components were extracted, including type (in-person vs. technology-based), content (diet or physical activity or both), form (individual session vs. group session), duration, intensity, evaluation time point, and program delivery. A total of 12 studies met the inclusion criteria. The mean annual type 2 diabetes mellitus (T2DM) incidence of the intervention group was lower than that of the comparison group (6.0% vs. 9.3%), although there was no statistical difference between the two groups. About 50% of these studies and two-thirds of studies, respectively, reported a significant decrease in insulin resistance-related measures and weight-related measures in the intervention group compared with the comparison group. The median intervention duration and study length were 6 months. Postpartum lifestyle interventions can be effective in reducing T2DM development and insulin resistance, and decrease weight in women with GDM history, regardless of the intervention types (technology-based or in-person). Effective interventions typically include dietary changes while some physical activity changes can also improve outcomes. However, more interventions with long-term efficacy evaluation are warranted.
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The Relationship Between Shift Work and Metabolic Risk Factors: A Systematic Review of Longitudinal Studies.
Proper, KI, van de Langenberg, D, Rodenburg, W, Vermeulen, RCH, van der Beek, AJ, van Steeg, H, van Kerkhof, LWM
American journal of preventive medicine. 2016;(5):e147-e157
Abstract
CONTEXT Although the metabolic health effects of shift work have been extensively studied, a systematic synthesis of the available research is lacking. This review aimed to systematically summarize the available evidence of longitudinal studies linking shift work with metabolic risk factors. EVIDENCE ACQUISITION A systematic literature search was performed in 2015. Studies were included if (1) they had a longitudinal design; (2) shift work was studied as the exposure; and (3) the outcome involved a metabolic risk factor, including anthropometric, blood glucose, blood lipid, or blood pressure measures. EVIDENCE SYNTHESIS Eligible studies were assessed for their methodologic quality in 2015. A best-evidence synthesis was used to draw conclusions per outcome. Thirty-nine articles describing 22 studies were included. Strong evidence was found for a relation between shift work and increased body weight/BMI, risk for overweight, and impaired glucose tolerance. For the remaining outcomes, there was insufficient evidence. CONCLUSIONS Shift work seems to be associated with body weight gain, risk for overweight, and impaired glucose tolerance. Overall, lack of high-methodologic quality studies and inconsistency in findings led to insufficient evidence in assessing the relation between shift work and other metabolic risk factors. To strengthen the evidence, more high-quality longitudinal studies that provide more information on the shift work schedule (e.g., frequency of night shifts, duration in years) are needed. Further, research to the (mediating) role of lifestyle behaviors in the health effects of shift work is recommended, as this may offer potential for preventive strategies.
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Azelnidipine and glucose tolerance: possible indications and treatment selection for hypertensive patients with metabolic disorders.
Shimada, K, Miyauchi, K, Daida, H
Expert review of cardiovascular therapy. 2015;(1):23-31
Abstract
Azelnidipine is a unique dihydropyridine calcium channel blocker with selectivity for L-type calcium channels that has been launched for the treatment of hypertension. Azelnidipine exhibits long-acting blood pressure-lowering effects without increasing heart rate. High blood pressure is associated with many metabolic disorders, including glucose intolerance and insulin resistance. Antihypertensive medications that interfere with various steps in the renin-angiotensin system improve glucose tolerance and insulin resistance; however, the effects of calcium channel blockers on glucose metabolism and insulin resistance remain controversial. Recent studies have demonstrated that azelnidipine could improve insulin resistance and glucose tolerance by potentially inhibiting sympathetic nerve activity. In addition, azelnidipine exhibits anti-inflammatory and anti-oxidative effects, suggesting that it is a beneficial antihypertensive agent with anti-atherogenic and cardioprotective effects for the treatment of not only hypertensive patients with glucose intolerance, but also those with metabolic disorders.
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Cystic fibrosis-related diabetes: a distinct condition.
Cano Megías, M, González Albarrán, O
Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion. 2015;(1):38-44
Abstract
Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis.