Insulin glargine effectively achieves glycemic control and improves insulin resistance in patients with early type 2 diabetes that exhibit a high risk for cardiovascular disease

Background and objectivesIn people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions.Design, setting, participants, & measurementsThe Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%–7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors.ResultsThere were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively).ConclusionsIn people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.

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Switching to Insulin Glargine 300 U/mL (Gla-300) Improves Glycemic Control and Reduces Nocturnal Hypoglycemia in Patients (Pts) with Type 2 Diabetes (T2DM) on Basal Insulin Supported Oral Therapy (BOT)

Diabetes ◽

10.2337/db18-1020-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1020-P ◽

Cited By ~ 2

Author(s):

JOCHEN SEUFERT ◽

ANDREAS FRITSCHE ◽

HELMUT ANDERTEN ◽

KATRIN PEGELOW ◽

STEFAN PSCHERER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Insulin Glargine ◽

Basal Insulin ◽

Oral Therapy ◽

Nocturnal Hypoglycemia

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Efficacy and cardiovascular safety of Thiazolidinediones

Current Drug Safety ◽

10.2174/1574886315666201026125530 ◽

2020 ◽

Vol 15 ◽

Author(s):

Raveendran Arkiath Veettil ◽

Cornelius James Fernandez ◽

Koshy Jacob

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Glucose Transporter ◽

Cell Function ◽

Cardiovascular Safety ◽

Cardiovascular Outcome Trials ◽

Glucose Transporter 2 ◽

Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

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Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001413 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001413

Author(s):

Jonathan Yap ◽

Kamalesh Anbalakan ◽

Wan Ting Tay ◽

Daniel Ting ◽

Carol Yim Cheung ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Glycemic Control ◽

Microvascular Complications ◽

Population Based ◽

Cardiovascular Outcomes ◽

Microvascular Complication ◽

The Impact ◽

Hba1c Levels

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05).ConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.

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Insulin resistance limits corneal nerve regeneration in patients with Type 2 diabetes undergoing intensive glycemic control

Journal of Diabetes Investigation ◽

10.1111/jdi.13582 ◽

2021 ◽

Author(s):

Georgios Ponirakis ◽

Muhammad A. Abdul‐Ghani ◽

Amin Jayyousi ◽

Mahmoud A. Zirie ◽

Salma Al‐Mohannadi ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glycemic Control ◽

Nerve Regeneration ◽

Intensive Glycemic Control ◽

Corneal Nerve

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Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22157797 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7797

Author(s):

Joseph A. M. J. L. Janssen

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Insulin Secretion ◽

Early Stage ◽

Insulin Clearance ◽

Future Research ◽

Age Related ◽

Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

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Impact of short‐term bilberry supplementation on glycemic control, cardiovascular disease risk factors, and antioxidant status in Chinese patients with type 2 diabetes

Phytotherapy Research ◽

10.1002/ptr.7038 ◽

2021 ◽

Author(s):

Sze Wa Chan ◽

Tanya T. W. Chu ◽

Siu Wai Choi ◽

Iris F. F. Benzie ◽

Brian Tomlinson

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Glycemic Control ◽

Antioxidant Status ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Chinese Patients ◽

Short Term

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The effects of metformin plus sulfonylurea therapy on clinical features of the metabolic syndrome

Medicinski pregled ◽

10.2298/mpns1010611k ◽

2010 ◽

Vol 63 (9-10) ◽

pp. 611-615 ◽

Cited By ~ 1

Author(s):

Branka Koprivica ◽

Teodora Beljic-Zivkovic ◽

Tatjana Ille

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Body Mass Index ◽

Waist Circumference ◽

Glycemic Control ◽

Body Mass ◽

Combined Therapy

Introduction. Insulin resistance is a well-known leading factor in the development of metabolic syndrome. The aim of this study was to evaluate metabolic effects of metformin added to sulfonylurea in unsuccessfully treated type 2 diabetic patients with metabolic syndrome. Material and methods. A group of thirty subjects, with type 2 diabetes, secondary sulfonylurea failure and metabolic syndrome were administered the combined therapy of sulfonylurea plus metformin for six months. Metformin 2000 mg/d was added to previously used sulfonylurea agent in maximum daily dose. Antihypertensive and hypolipemic therapy was not changed. The following parameters were assessed at the beginning and after six months of therapy: glycemic control, body mass index, waist circumference, blood pressure, triglycerides, total cholesterol and its fractions, homeostatic models for evaluation of insulin resistance and secretion (HOMA R, HOMA B) and C- peptide. Results. Glycemic control was significantly improved after six months of the combined therapy: (fasting 7.89 vs. 10.61 mmol/l. p<0.01; postprandial 11.12 vs. 12.61 mmol/l. p<0.01, p<0.01; glycosylated hemoglobin 6.81 vs. 8.83%. p<0.01). the body mass index and waist circumference were significantly lower (26.7 vs. 27.8 kg/m2, p<0.01 and 99.7 vs. 101.4 cm for men, p<0.01; 87.2 vs. 88.5 for women, p<0.01). Fasting plasma triglycerides decreased from 3.37 to 2.45 mmol/l (p<0.001) and HOMA R from 7.04 to 5.23 (p<0.001). No treatment effects were observed on blood pressure, cholesterol, and residual insulin secretion. Conclusion. Administration of metformin in type 2 diabetes with metabolic syndrome decreased cardiovascular risk factors by reducing glycemia, triglycerides, BMI, central obesity and insulin resistance.

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