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1.
BMJ. 2018 Nov 21;363:k4641. doi: 10.1136/bmj.k4641.

Rotating night shift work and adherence to unhealthy lifestyle in predicting risk of type 2 diabetes: results from two large US cohorts of female nurses.

Author information

1
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China zshan@hsph.harvard.edu.
2
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
3
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
4
Department of Occupational and Environmental Health, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
5
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
6
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
7
Department of Epidemiology, Center for Public Health, Medical University of Vienna, Austria.

Abstract

OBJECTIVES:

To prospectively evaluate the joint association of duration of rotating night shift work and lifestyle factors with risk of type 2 diabetes risk, and to quantitatively decompose this joint association to rotating night shift work only, to lifestyle only, and to their interaction.

DESIGN:

Prospective cohort study.

SETTING:

Nurses' Health Study (1988-2012) and Nurses' Health Study II (1991-2013).

PARTICIPANTS:

143 410 women without type 2 diabetes, cardiovascular disease, or cancer at baseline.

EXPOSURES:

Rotating night shift work was defined as at least three night shifts per month in addition to day and evening shifts in that month. Unhealthy lifestyles included current smoking, physical activity levels below 30 minutes per day at moderate to vigorous intensity, diet in the bottom three fifths of the Alternate Healthy Eating Index score, and body mass index of 25 or above.

MAIN OUTCOME MEASURES:

Incident cases of type 2 diabetes were identified through self report and validated by a supplementary questionnaire.

RESULTS:

During 22-24 years of follow-up, 10 915 cases of incident type 2 diabetes occurred. The multivariable adjusted hazard ratios for type 2 diabetes were 1.31 (95% confidence interval 1.19 to 1.44) per five year increment of duration of rotating night shift work and 2.30 (1.88 to 2.83) per unhealthy lifestyle factor (ever smoking, low diet quality, low physical activity, and overweight or obesity). For the joint association of per five year increment rotating night shift work and per unhealthy lifestyle factor with type 2 diabetes, the hazard ratio was 2.83 (2.15 to 3.73) with a significant additive interaction (P for interaction <0.001). The proportions of the joint association were 17.1% (14.0% to 20.8%) for rotating night shift work alone, 71.2% (66.9% to 75.8%) for unhealthy lifestyle alone, and 11.3% (7.3% to 17.3%) for their additive interaction.

CONCLUSIONS:

Among female nurses, both rotating night shift work and unhealthy lifestyle were associated with a higher risk of type 2 diabetes. The excess risk of rotating night shift work combined with unhealthy lifestyle was higher than the addition of risk associated with each individual factor. These findings suggest that most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work other than those detailed above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

2.
BMJ. 2018 Nov 20;363:k4723. doi: 10.1136/bmj.k4723.

Monitoring glycaemic control in patients with diabetes mellitus.

Author information

1
Department of Blood Sciences, Royal Lancaster Infirmary & Furness General Hospital, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, UK Ravinder.Sodi@mbht.nhs.uk ravsodi@yahoo.com.
2
Lancaster Medical School, University of Lancaster, Lancaster, UK.
3
McKay and Partners, Wishaw, UK.
4
Department of Medicine, Royal Lancaster Infirmary, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, UK.
PMID:
30459149
DOI:
10.1136/bmj.k4723
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Conflict of interest statement

Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.

3.
Diabet Med. 2018 Nov 22. doi: 10.1111/dme.13866. [Epub ahead of print]

Mealtime fast-acting insulin aspart versus insulin aspart for controlling postprandial hyperglycaemia in people with insulin-resistant Type 2 diabetes.

Author information

1
Division of Endocrinology and Metabolism, University of Alberta, Edmonton, Alberta, Canada.
2
Wrexham Academic Unit, Bangor University, Bangor, UK.
3
Novo Nordisk Inc., Plainsboro, NJ.
4
Atlanta Diabetes Associates, Atlanta, GA, USA.

Abstract

AIM:

This post hoc analysis explored whether mealtime fast-acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin.

METHODS:

A post hoc, post-randomization, subgroup analysis of a 26-week, randomized, double-blind, treat-to-target trial (onset 2) that compared mealtime fast-acting insulin aspart vs. mealtime insulin aspart, both in a basal-bolus regimen, in people with Type 2 diabetes uncontrolled on basal insulin therapy and metformin. At the end of trial, the impact of fast-acting insulin aspart and insulin aspart on PPG control was assessed with a standard liquid meal test and participants were grouped into three post-randomization subgroups: meal test bolus insulin dose ≤ 10 units per dose (n = 171), > 10-20 units per dose (n = 289) and > 20 units per dose (n = 146).

RESULTS:

A statistically significant treatment difference in favour of fast-acting insulin aspart vs. insulin aspart was observed for the change in PPG increment at all post-meal time points (from 1 to 4 h) for those in the > 20 units bolus insulin subgroup. There was no difference in the magnitude of change from baseline in HbA1c level between fast-acting insulin aspart and insulin aspart in any of the bolus insulin dose subgroups (data herein).

CONCLUSION:

Fast-acting insulin aspart may hold promise as a more effective treatment compared with insulin aspart for controlling PPG in people with insulin-resistant Type 2 diabetes.

PMID:
30466191
DOI:
10.1111/dme.13866
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4.
Diabet Med. 2018 Nov 22. doi: 10.1111/dme.13867. [Epub ahead of print]

How do we identify people at high risk of Type 2 diabetes and help prevent the condition from developing?

Author information

1
Public Health England, London, UK.
2
NHS England, Imperial College Healthcare NHS Trust, Imperial College London, London, UK.

Abstract

AIMS:

To review the evidence regarding the identification of those at high risk of Type 2 diabetes and the conceptual and clinical criteria defining high risk, the prevention or delay of onset of Type 2 diabetes through lifestyle interventions, and the evolution of evidence from efficacy trials, through effectiveness trials in real-world settings, to implementation programmes at scale.

METHOD:

The wide scope of this review precluded a systematic approach, therefore, we present a narrative review that highlights key themes and contemporary developments, drawing on landmark studies, previous systematic and expert reviews, and previous meta-analyses.

RESULTS:

While the diagnostic thresholds for Type 2 diabetes are accepted, international consensus on whether, and how, to classify those at high risk of Type 2 diabetes has not been achieved. There is ongoing debate about which laboratory test to use and each test's corresponding inclusion threshold, about where the balance of clinical benefits and harms sit when defining thresholds, and about how affordability of subsequent preventative interventions might influence the derivation of such thresholds within any particular population. A remarkable international effort has seen the evolution of interventions for those at high risk move from efficacy trials, through effectiveness trials, to implementation at scale, and the evidence supporting each stage is reviewed.

CONCLUSIONS:

To achieve healthcare system sustainability, many countries are now focusing on disease prevention. To complement population-level interventions that address the obesogenic environment, lifestyle interventions that empower individuals at high risk of Type 2 diabetes to modify this risk beneficially are now being implemented at scale.

PMID:
30466172
DOI:
10.1111/dme.13867
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5.
Diabet Med. 2018 Nov 15. doi: 10.1111/dme.13864. [Epub ahead of print]

An intravenous insulin protocol designed for pregnancy reduces neonatal hypoglycaemia following betamethasone administration in women with gestational diabetes.

Author information

1
Department of Endocrinology and Diabetes, John Hunter Hospital, Newcastle, Australia.
2
School of Medicine and Public Health, University of New castle, Newcastle, Australia.
3
Department of Maternity and Gynaecology, John Hunter Hospital, Newcastle, Australia.

Abstract

AIMS:

Marked hyperglycaemia is common following betamethasone administration in women with gestational diabetes (GDM), and may contribute to neonatal hypoglycaemia. Validated protocols to deliver glycaemic stability following betamethasone are lacking. We hypothesized that an intravenous insulin (IVI) protocol for pregnancy-specific glycaemic targets (Pregnancy-IVI) would achieve greater at-target glycaemic control than a generic adult intravenous insulin protocol (Adult-IVI), and may reduce neonatal hypoglycaemia.

METHODS:

A retrospective cohort study of the performance Adult-IVI and Pregnancy-IVI following betamethasone in GDM, sequentially implemented at a tertiary hospital, without change in indication for IVI. Cases were identified by electronic record search. Primary outcome was percentage of on-IVI time with at-target glycaemia [blood glucose level (BGL) 3.8-7 mmol/l]. Secondary outcomes were time with critical hyperglycaemia (BGL > 10 mmol/l), occurrence of maternal hypoglycaemia (BGL < 3.8 mmol/l), and incidence of neonatal hypoglycaemia (BGL ≤ 2.5 mmol/l) if betamethasone was administered within 48 h of birth.

RESULTS:

The cohorts comprised 151 women (Adult-IVI n = 86; Pregnancy-IVI n = 65). The primary outcome was 68% time-at-target [95% confidence interval (CI) 64-71%) for Pregnancy-IVI compared with 55% (95% CI 50-60%) for Adult-IVI (P = 0.0002). Critical maternal hyperglycaemia (0% vs. 2%, P = 0.02) and hypoglycaemia (2% vs. 12%, P = 0.02) were both lower with Pregnancy-IVI than Adult-IVI. Neonatal hypoglycaemia was less common after Pregnancy-IVI (29%) than after Adult-IVI (54%, P = 0.03). A multiple logistic regression model adjusting for potential confounders gave an odds ratio for neonatal hypoglycaemia with Pregnancy-IVI of 0.27 (95% CI 0.10-0.76, P = 0.01).

CONCLUSIONS:

An IVI protocol designed for pregnancy effectively controlled maternal hyperglycaemia following betamethasone administration in GDM. This is the first intervention to show a reduction in betamethasone-associated neonatal hypoglycaemia, linked with optimum maternal glycaemic control.

PMID:
30443983
DOI:
10.1111/dme.13864
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6.
Diabetes. 2018 Dec;67(12):e2-e3. doi: 10.2337/dbi18-0037.

Response to Comment on Bu et al. Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages. Diabetes 2018;67:1761-1772.

Author information

1
Laboratory of Molecular Endocrinology and Metabolism, Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, and Research Program for Signal Transduction, Division of Endocrinology, Metabolism and Signal Research, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Japan tizumi@gunma-u.ac.jp.

Publication type

Publication type

7.
Diabetes. 2018 Dec;67(12):e1. doi: 10.2337/db18-0984.

Comment on Bu et al. Insulin Regulates Lipolysis and Fat Mass by Upregulating Growth/Differentiation Factor 3 in Adipose Tissue Macrophages. Diabetes 2018;67:1761-1772.

Author information

1
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Life Sciences Institute, National University of Singapore, Singapore; and Department of Physiology, National University of Singapore, Singapore carlos.ibanez@ki.se.
PMID:
30459253
DOI:
10.2337/db18-0984
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Publication type

8.
Diabetes. 2018 Dec;67(12):2485-2493. doi: 10.2337/dbi18-0024.

Targeting Metabolism, Insulin Resistance, and Diabetes to Treat Nonalcoholic Steatohepatitis.

Author information

1
Center for Human Nutrition, Division of Geriatrics and Nutritional Sciences, John T. Milliken Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO bfinck@wustl.edu.

Abstract

Obesity, insulin resistance, and diabetes are strongly linked to the accumulation of excessive lipids in the liver parenchyma, a condition known as nonalcoholic fatty liver disease (NAFLD). Given its association with obesity and related metabolic diseases, it is not surprising that the prevalence of NAFLD has dramatically increased in the past few decades. NAFLD has become the most common liver disease in many areas of the world. The term, NAFLD, encompasses a spectrum of disorders that ranges from simple steatosis to steatosis with inflammatory lesions (nonalcoholic steatohepatitis [NASH]). Although simple steatosis might be relatively benign, epidemiologic studies have linked NASH to greatly increased risk of developing cirrhosis and hepatocellular carcinoma. Yet despite this, there are no approved treatments for the disease, and it remains a significant unmet medical need. This Perspective will review some of the relevant literature on the topic and examine approved and experimental NASH therapeutic concepts that target intermediary metabolism, insulin resistance, and diabetes to treat this emerging public health problem.

PMID:
30459251
PMCID:
PMC6245219
[Available on 2019-12-01]
DOI:
10.2337/dbi18-0024
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9.
Diabetes. 2018 Dec;67(12):2483-2484. doi: 10.2337/db18-ti12.

In This Issue of Diabetes.

[No authors listed]
PMID:
30459250
DOI:
10.2337/db18-ti12
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12.
Diabetes Care. 2018 Dec;41(12):2603-2609. doi: 10.2337/dc18-0755.

Fasiglifam-Induced Liver Injury in Patients With Type 2 Diabetes: Results of a Randomized Controlled Cardiovascular Outcomes Safety Trial.

Author information

1
Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH menonv@ccf.org.
2
Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH.
3
South Australian Heart and Medical Research Institute, The University of Adelaide, Adelaide, Australia.
4
Division of Cardiology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX.
5
Cytel, Inc., Cambridge, MA.
6
Dallas Diabetes Research Center at Medical City, Dallas, TX.
7
Takeda Development Center Americas, Inc., Deerfield, IL.

Abstract

OBJECTIVE:

To evaluate the cardiovascular (CV) safety of fasiglifam, a first-in-man G-protein-coupled receptor 40 (GPR40) agonist, in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS:

A phase 3 multicenter randomized double-blind placebo-controlled two-arm trial was intended to randomize 5,000 participants with type 2 diabetes at high CV risk to fasiglifam or placebo. The primary objective of the trial was to rule out an upper noninferiority bound >1.3 for a one-sided 97.5% confidence limit of the hazard ratio (HR) for CV composite events during treatment with fasiglifam compared with placebo. The primary outcome was the time to first occurrence of any component of the major adverse CV event composite of CV death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for unstable angina.

RESULTS:

The study enrolled 3,207 participants but was terminated because of liver safety concerns. Increased rates of liver enzyme elevation (AST/ALT ≥3-5 × upper limit of normal [ULN]) with fasiglifam were observed. The incidence of ALT or AST ≥3 × ULN with fasiglifam compared with placebo was 2.1% vs. 0.5%, P < 0.001, and the incidence for ≥10 × ULN was 0.31% vs. 0.06%, P < 0.001. A primary CV composite outcome occurred in 40 participants, 2.5% each in the fasiglifam and placebo arms at 12 months (HR 1.05; 95% CI 0.67, 1.63).

CONCLUSIONS:

Development of fasiglifam was terminated due to concerns of drug-induced liver injury. Performance of a U.S. Food and Drug Administration-mandated CV outcomes trial supported the termination of the fasiglifam clinical program.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01609582.

PMID:
30459247
DOI:
10.2337/dc18-0755
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13.
Diabetes Care. 2018 Dec;41(12):2448-2452. doi: 10.2337/dci18-0042.

John A. Galloway, MD, FACP: A Pharmaceutical Physician and Leader in Diabetes Therapy.

Author information

1
Diabetes and CardioMetabolic Disease Solutions Group, Carmel, Indiana jhandersonjr@msn.com.
15.
Diabetes Care. 2018 Dec;41(12):2441-2443. doi: 10.2337/dci18-0034.

The Dynamic Origins of Type 1 Diabetes.

Author information

1
Department of Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, U.K. r.d.g.leslie@qmul.ac.uk grants@chop.edu.
2
Divisions of Human Genetics and Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA r.d.g.leslie@qmul.ac.uk grants@chop.edu.
3
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
4
Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
5
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
PMID:
30459244
PMCID:
PMC6245204
[Available on 2019-12-01]
DOI:
10.2337/dci18-0034
[Indexed for MEDLINE]
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16.
Diabetes Care. 2018 Dec;41(12):2439-2440. doi: 10.2337/dc18-ti12.

In This Issue of Diabetes Care.

[No authors listed]
PMID:
30459243
DOI:
10.2337/dc18-ti12
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17.
Diabetes Care. 2018 Nov 19. pii: dc181560. doi: 10.2337/dc18-1560. [Epub ahead of print]

Improvement in Neuropathy Outcomes With Normalizing HbA1c in Patients With Type 2 Diabetes.

Author information

1
Ishibashi Clinic, Hiroshima, Japan.
2
University of Exeter Medical School, Exeter, U.K. m.tavakoli@exeter.ac.uk.

Abstract

OBJECTIVE:

To investigate the impact of normalizing HbA1c by extensive HbA1c control (EHC) on neuropathy outcome measures (NOMs), nephropathy, and retinopathy in type 2 diabetes.

RESEARCH DESIGN AND METHODS:

Detailed clinical and neurological examinations were performed in two cohorts of 38 patients with uncontrolled type 2 diabetes patients (HbA1c 9.6% [81.4 mmol/mol]) at baseline and after glycemic control (GC) with or without EHC by diet restriction and hypoglycemic agents over 4 years along with 48 control subjects with normal glucose tolerance (NGT) and 34 subjects with impaired glucose tolerance (IGT) only at baseline. EHC patients, control subjects, and subjects with IGT underwent oral glucose tolerance tests. Glycemic variability (GV) was evaluated by SD and coefficient of variation of monthly measured HbA1c levels and casual plasma glucose.

RESULTS:

In the EHC cohort, HbA1c levels over 4.3 years and the last 2 years improved to 6.1% (43.2 mmol/mol) and 5.8% (39.9 mmol/mol) with 7.3 kg body wt reduction, and 50 and 28.9% of patients returned to IGT and NGT, respectively, at end point. Baseline neurophysiological and corneal nerve fiber (CNF) measures were impaired in patients. Normalized HbA1c with EHC improved neurophysiological and CNF measures to be similar for those for IGT, while GC without EHC (mean HbA1c level 7.0% [53.5 mmol/mol]) improved only vibration perception. The mean normalized HbA1c levels by EHC determined NOM improvements. The high GV and baseline HbA1c levels compromised NOMs. Albumin excretion rate significantly decreased, while retinopathy severity and frequency insignificantly worsened on EHC.

CONCLUSIONS:

Normalizing HbA1c in type 2 diabetes of short duration improves microvascular complications including neuropathy and nephropathy more effectively than standard GC but not retinopathy.

PMID:
30455338
DOI:
10.2337/dc18-1560
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18.
Diabetes Care. 2018 Nov 19. pii: dc180914. doi: 10.2337/dc18-0914. [Epub ahead of print]

HbA1c, Insulin Resistance, and β-Cell Function in Relation to Cognitive Function in Type 2 Diabetes: The CAROLINA Cognition Substudy.

Author information

1
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands j.janssen-9@umcutrecht.nl.
2
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
3
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
5
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Division of Endocrinology, University of Toronto, Toronto, Canada.
6
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC.
7
Department of Internal Medicine and Cardiovascular Research Institute, Maastricht University Medical Center+, Maastricht, the Netherlands.
8
Global Biometrics and Data Management, Boehringer Ingelheim, Ingelheim, Germany.
9
Clinical Development, Therapeutic Area CardioMetabolic, Boehringer Ingelheim, Asker, Norway.
PMID:
30455337
DOI:
10.2337/dc18-0914
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19.
Diabetes Care. 2018 Nov 19. pii: dc181475. doi: 10.2337/dc18-1475. [Epub ahead of print]

Optimal Insulin Correction Factor in Post-High-Intensity Exercise Hyperglycemia in Adults With Type 1 Diabetes: The FIT Study.

Author information

1
LMC Diabetes & Endocrinology, Toronto, Ontario, Canada ronnie.aronson@lmc.ca.
2
LMC Diabetes & Endocrinology, Toronto, Ontario, Canada.
3
School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.

Abstract

OBJECTIVE:

Postexercise hyperglycemia, following high-intensity interval training (HIIT) in patients with type 1 diabetes (T1D), is largely underrecognized by the clinical community and generally undertreated. The aim of this study was to compare four multipliers of an individual's insulin correction factor (ICF) to treat post-HIIT hyperglycemia.

RESEARCH DESIGN AND METHODS:

The FIT study had a randomized, crossover design in physically active subjects with T1D (mean ± SD age 34.9 ± 10.1 years, BMI 25.5 ± 2.5 kg/m2, and HbA1c 7.2 ± 0.9%) using multiple daily injections. Following an 8-week optimization period, with 300 units/mL insulin glargine used as the basal insulin, subjects performed four weekly sessions of 25 min of HIIT. If hyperglycemia (>8.0 mmol/L) resulted, subjects received a bolus insulin correction 15 min post-HIIT, based on their own ICF, adjusted by one of four multipliers: 0, 50, 100, or 150%.

RESULTS:

Seventeen subjects completed 71 exercise trials, of which 64 (90%) resulted in hyperglycemia. At 40 min postexercise, plasma glucose (PG) increased from mean ± SD 8.8 ± 1.0 mmol/L at baseline to 12.7 ± 2.4 mmol/L (increase of 3.8 ± 1.5 mmol/L). After correction, adjusted mean ± SE PG was significantly reduced for the 50% (-2.3 ± 0.8 mmol/L, P < 0.01), 100% (-4.7 ± 0.8 mmol/L, P < 0.001), and 150% (-5.3 ± 0.8 mmol/L, P < 0.001) arms but had increased further in the 0% correction arm. Both the 100 and 150% corrections were more effective than the 50% correction (P < 0.01 and P < 0.001, respectively) but were not different from each other. Hypoglycemia was rare.

CONCLUSIONS:

In post-HIIT hyperglycemia, correction based on a patient's usual ICF is safe and effective. Optimal PG reduction, with minimal hypoglycemia, occurred in the 100 and 150% correction arms.

PMID:
30455336
DOI:
10.2337/dc18-1475
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20.
Diabetes Care. 2018 Nov 19. pii: dc181144. doi: 10.2337/dc18-1144. [Epub ahead of print]

Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial.

Author information

1
Department of Medicine, University of Maryland, Baltimore, MD sdavis@som.umaryland.edu.
2
U.S. Department of Veterans Affairs, Washington, DC.

Abstract

OBJECTIVE:

To determine the risk factors for severe hypoglycemia and the association between severe hypoglycemia and serious cardiovascular adverse events and cardiovascular and all-cause mortality in the Veterans Affairs Diabetes Trial (VADT).

RESEARCH DESIGN AND METHODS:

This post hoc analysis of data from the VADT included 1,791 military veterans (age 60.5 ± 9.0 years) with suboptimally controlled type 2 diabetes (HbA1c 9.4 ± 2.0%) of 11.5 ± 7.5 years disease duration with or without known cardiovascular disease and additional cardiovascular risk factors. Participants were randomized to intensive (HbA1c <7.0%) versus standard (HbA1c <8.5%) glucose control.

RESULTS:

The rate of severe hypoglycemia in the intensive treatment group was 10.3 per 100 patient-years compared with 3.7 per 100 patient-years in the standard treatment group (P < 0.001). In multivariable analysis, insulin use at baseline (P = 0.02), proteinuria (P = 0.009), and autonomic neuropathy (P = 0.01) were independent risk factors for severe hypoglycemia, and higher BMI was protective (P = 0.017). Severe hypoglycemia within the past 3 months was associated with an increased risk of serious cardiovascular events (P = 0.032), cardiovascular mortality (P = 0.012), and total mortality (P = 0.024). However, there was a relatively greater increased risk for total mortality in the standard group compared with the intensive group (P = 0.019). The association between severe hypoglycemia and cardiovascular events increased significantly as overall cardiovascular risk increased (P = 0.012).

CONCLUSIONS:

Severe hypoglycemic episodes within the previous 3 months were associated with increased risk for major cardiovascular events and cardiovascular and all-cause mortality regardless of glycemic treatment group assignment. Standard therapy further increased the risk for all-cause mortality after severe hypoglycemia.

PMID:
30455335
DOI:
10.2337/dc18-1144
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