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

Increased dietary fibre intake is a component of prudent dietary advice, although the mechanism of its beneficial effect is unclear. Furthermore, plasma lipoprotein response to dietary fibre seems to vary both between individuals and according to the type of fibre consumed. Two common genetic variants, A54 and T54, of the intestinal fatty acid-binding protein gene (FABP2) have different in vitro binding affinities for long-chain fatty acids. We have hypothesized that variation in FABP2 would be associated with interindividual variation in the response of plasma lipoproteins to either dietary soluble or insoluble fibre. We studied 43 subjects who participated in a year-long cross-over study of the effect of insoluble and soluble fibre on plasma lipoproteins. We tested for associations between FABP2 genotypes and the response of plasma lipoproteins to dietary fibre. When compared with subjects homozygous for FABP2 A54, we found that subjects with FABP2 T54 had significantly greater decreases in plasma total and low-density lipoprotein (LDL)-cholesterol and apoB during the period when the diet was high in soluble fibre than during the period when the diet was high in insoluble fibre. Furthermore, compared with subjects with the FABP2 A54 allele, subjects with the FABP2 T54 allele had significantly lower secretion of total fecal bile acids, but this did not increase with dietary soluble fibre. Genetic variation in FABP2 may thus contribute to interindividual variation in the response of plasma lipoproteins to different dietary fibres, but the mechanism does not appear to be related to increases in fecal bile acid secretion.

Intestinal fatty acid-binding protein variation associated with variation in the response of plasma lipoproteins to dietary fibre

Inulin increases short-term markers for colonic fermentation similarly in healthy and hyperinsulinaemic humans

Inulin increases short-term markers for colonic fermentation similarly in healthy and hyperinsulinaemic humans.

Barley has a low glycemic index (GI), but it is unknown whether its GI is affected by variation in carbohydrate composition in different cultivars and by food processing and food form. To examine the effect of these factors on GI, 9 barley cultivars varying in amylose and β-glucan content were studied in 3 experiments in separate groups of 10 healthy participants. In Expt. 1, 3 barley cultivars underwent 2 levels of processing: hull removal [whole-grain (WG)] and bran, germ, and crease removal [white pearled (WP)]. GI varied by cultivar (CDC Fibar vs. AC Parkhill, [mean ± SEM]: 26 ± 3 vs. 53 ± 4, respectively; P < 0.05) and pearling (WG vs. WP: 26 ± 4 vs. 35 ± 3, respectively; P < 0.05) with no cultivar × pearling interaction. In Expt. 2, the GI of 7 WG cultivars ranged from 21 ± 4 to 36 ± 8 (P = 0.09). In Expt. 3, WG and WP AC Parkhill and Celebrity cultivars were ground and made into wet pasta. The GI of AC Parkhill pasta (69 ± 3) was similar to that of Celebrity pasta (64 ± 4) but, unlike in Expt. 1, the GI of WP pasta (61 ± 3) was less than that of WG pasta (72 ± 4) (P < 0.05). Pooled data from Expts. 1 and 2 showed that GI was correlated with total fiber (r = -0.75, P = 0.002) but not with measures of starch characteristics. We conclude that the GI of barley is influenced by cultivar, processing, and food form but is not predicted by its content of amylose or other starch characteristics.

/pdf/barley-cultivar-kernel-composition-and-processing-affect-the-enwbhr22yl.pdf

Barley Cultivar, Kernel Composition, and Processing Affect the Glycemic Index

Colonic fermentation of dietary fiber may improve insulin sensitivity by the metabolic effects of short chain fatty acids (SCFA) in reducing free fatty acids (FFA). The main objectives of this study were to compare peripheral uptake of acetate (AC) in participants with normal (<40 pmol/l, NI) and high (⩾40 pmol/l, HI) plasma insulin, and the ability of AC to reduce FFA in both the groups. Overnight fasted NI (n=9) and HI (n=9) participants were given an intravenous (IV) infusion of 140 mmol/l sodium acetate at three different rates over 90 min. The total amount of AC infused was 51.85 mmols. AC clearance in NI participants was not significantly different than that in HI participants (2.11±0.23 vs 2.09±0.24 ml/min). FFA fell in both the groups, but rebounded to a greater extent in NI than HI participants (time × group interaction, P=0.001). Significant correlations between insulin resistance (IR) indices (homeostasis model assessment of insulin resistance (HOMA-IR), Matsuda and insulinogenic index) vs FFA rebound during IV AC infusion were also observed. These findings suggest that AC uptake is similar in both the groups. Participants with lower plasma insulin and lower IR indices had a greater FFA rebound. These results support the hypothesis that increasing AC concentrations in the systemic circulation may reduce lipolysis and plasma FFA concentrations and thus improve insulin sensitivity. More in-depth studies are needed to look at the effects of SCFA on FFA metabolism in insulin-resistant participants.

Thomas M.S. Wolever

Papers

Intestinal fatty acid-binding protein variation associated with variation in the response of plasma lipoproteins to dietary fibre

Inulin increases short-term markers for colonic fermentation similarly in healthy and hyperinsulinaemic humans.

Barley Cultivar, Kernel Composition, and Processing Affect the Glycemic Index

Intravenous Acetate Elicits a Greater Free Fatty Acid Rebound in Normal than Hyperinsulinaemic Humans

Dietary fibre and glucose tolerance importance of viscosity.