Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

BACKGROUND
Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial.


METHODS
3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy.


FINDINGS
Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg).


INTERPRETATION
Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)

WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

Resume Il est generalement admis que les regimes entrainant de faibles reponses glycemiques et insulinemiques augmentent la satiete, limitent la prise de poids et/ou augmentent la perte de poids. Ces effets ont egalement ete attribues aux aliments de faible index glycemique (IG) et/ou de faible index insulinemique (II). En matiere de perte de poids, il existe des preuves en faveur des aliments de faible IG par rapport a une reduction moderee de la consommation de glucides. Les mecanismes impliques ne sont toutefois pas clairs. Un aliment peut presenter un faible IG pour differentes raisons, telles que la presence de fructose ou de fibres alimentaires, la nature de l’amidon ou la taille des particules ; ces facteurs peuvent ne pas intervenir de la meme maniere sur le poids corporel. Les resultats d’etudes suggerant que les aliments de faible IG augmentent la satiete a court terme et reduisent la prise alimentaire a court terme sont incoherents et souvent perturbes par des facteurs autres que des differences de la reponse glycemique. Par consequent, il n’est pas possible d’imputer les differences de satiete/prise alimentaire observees a des differences des valeurs de la glycemie en tant que telles. Une insulinemie elevee est souvent decrite comme entrainant une augmentation du poids corporel parce que favorisant le stockage des graisses plutot que leur oxydation. Cependant, il est prouve que des adultes avec une insulinemie elevee ont une prise alimentaire plus faible et prennent moins de poids que des adultes presentant une insulinemie normale. Les aliments amylaces de faible IG peuvent participer a la regulation du poids corporel en raison d’une reduction du taux de digestion de l’amidon, conduisant a une reduction de l’absorption de l’energie et a une augmentation de la fermentation colique. A son tour cette fermentation peut avoir des effets directs et indirects sur les hormones de l’intestin, du pancreas et sur les hormones du tissu adipeux qui controlent la prise alimentaire et la depense energetique.

Index glycémique, index insulinémique et régulation du poids corporel

Comparison of postprandial glycemic and insulinemic response of allulose when consumed alone or when added to sucrose: A randomized controlled trial

Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student’s t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid.

/pdf/the-antioxidant-capacity-of-breast-milk-and-plasma-of-women-3rp9ugkz.pdf

The Antioxidant Capacity of Breast Milk and Plasma of Women with or without Gestational Diabetes Mellitus

Reply to UN Das

Abstract Objectives To estimate the time for hunger scores to return to baseline levels for the Control and high protein, high fiber shakes. Methods A total of 80 subjects were recruited for this double-blind, randomized, controlled study (50F:30 M; BMI 30.3 ± 3.7 kg/m2). Overnight fasted subjects consumed equicaloric portions (120 kcal) of the high protein, high fiber Chocolate Nutrisystem shake (NSh) and a low protein, low fiber chocolate beverage (Control). For pre-menopausal females, both visits were scheduled during the follicular phase of their menstrual cycle. The motivation-to-eat questionnaire was completed before and at 15. 30, 45, 60, 90, 120, 150, 180, 210 and 240 min after starting to consume the test meal. Throughout the 4.5 h visit, participants were seated quietly and were not be allowed to use any electronic devices. Time to baseline and differences in scores for the 4 satiety questions (Hunger, Desire to Eat, Prospective Consumption and Fullness) and the Average Appetite were analyzed. Results Five subjects dropped out and n = 75 were included in the final analysis. Per protocol analysis: Time to baseline for hunger scores after NSh, 183 ± 11 min, was the same as Control, 183 ± 12 min (n = 53; NS), however time to return to baseline for Fullness after NSh, 218 ± 10 min, was greater than Control, 198 ± 10 min, (n = 63; p = 0.036). When all 75 subjects were included in the analysis, there was no difference for hunger, but time to baseline for Fullness after NSh, 3 h and 20 min (200 ± 11 min) was significantly longer than Control, 2 h and 54 min (174 ± 11 min, p = 0.037). The % of subjects whose ratings were still above baseline after 4 h did not significantly differ for Hunger, Desire to Eat, Prospective Consumption or Average Appetite but was higher for Fullness after NSh, 44%, than Control, 28% (p = 0.041). Conclusions Hunger scores remained above baseline for over 3 h after a serving of Chocolate Nutrisystem shake and levels of fullness persisted for over 3.5 h. Fullness levels were significantly greater after consumption of the Nutrisystem shake than Control. The Nutrisystem shake may therefore be a helpful aid to increasing feelings of fullness. Funding Sources Nutrisystem Inc.

https://academic.oup.com/cdn/article-pdf/6/Supplement_1/446/44040951/nzac057.012.pdf

Effect of Consuming a High Protein, High Fiber Shake on Measures of Satiety: A Randomized, Controlled, Cross-Over Study in Healthy Overweight and Obese Subjects

Thomas M.S. Wolever

Papers

Index glycémique, index insulinémique et régulation du poids corporel

Comparison of postprandial glycemic and insulinemic response of allulose when consumed alone or when added to sucrose: A randomized controlled trial

The Antioxidant Capacity of Breast Milk and Plasma of Women with or without Gestational Diabetes Mellitus

Reply to UN Das

Effect of Consuming a High Protein, High Fiber Shake on Measures of Satiety: A Randomized, Controlled, Cross-Over Study in Healthy Overweight and Obese Subjects