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diabetes mellitus, type 2

Heart Failure With Preserved Ejection Fraction

Author/s: 
Redfield, Margaret, Borlaug, Barry

Importance Heart failure with preserved ejection fraction (HFpEF), defined as HF with an EF of 50% or higher at diagnosis, affects approximately 3 million people in the US and up to 32 million people worldwide. Patients with HFpEF are hospitalized approximately 1.4 times per year and have an annual mortality rate of approximately 15%.

Observations Risk factors for HFpEF include older age, hypertension, diabetes, dyslipidemia, and obesity. Approximately 65% of patients with HFpEF present with dyspnea and physical examination, chest radiographic, echocardiographic, or invasive hemodynamic evidence of HF with overt congestion (volume overload) at rest. Approximately 35% of patients with HFpEF present with “unexplained” dyspnea on exertion, meaning they do not have clear physical, radiographic, or echocardiographic signs of HF. These patients have elevated atrial pressures with exercise as measured with invasive hemodynamic stress testing or estimated with Doppler echocardiography stress testing. In unselected patients presenting with unexplained dyspnea, the H2FPEF score incorporating clinical (age, hypertension, obesity, atrial fibrillation status) and resting Doppler echocardiographic (estimated pulmonary artery systolic pressure or left atrial pressure) variables can assist with diagnosis (H2FPEF score range, 0-9; score >5 indicates more than 95% probability of HFpEF). Specific causes of the clinical syndrome of HF with normal EF other than HFpEF should be identified and treated, such as valvular, infiltrative, or pericardial disease. First-line pharmacologic therapy consists of sodium-glucose cotransporter type 2 inhibitors, such as dapagliflozin or empagliflozin, which reduced HF hospitalization or cardiovascular death by approximately 20% compared with placebo in randomized clinical trials. Compared with usual care, exercise training and diet-induced weight loss produced clinically meaningful increases in functional capacity and quality of life in randomized clinical trials. Diuretics (typically loop diuretics, such as furosemide or torsemide) should be prescribed to patients with overt congestion to improve symptoms. Education in HF self-care (eg, adherence to medications and dietary restrictions, monitoring of symptoms and vital signs) can help avoid HF decompensation.

Conclusions and Relevance Approximately 3 million people in the US have HFpEF. First-line therapy consists of sodium-glucose cotransporter type 2 inhibitors, exercise, HF self-care, loop diuretics as needed to maintain euvolemia, and weight loss for patients with obesity and HFpEF.

Keywords 
heart failure glucose Stroke Volume physical exertion hospitalization

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

Author/s: 
Pittas, A. G., Kawahara, T., Jorde, R., Dawson-Hughes, B., Vickery, E. M., Angellotti, E., Nelson, J., Trikalinos, T. A., Balk, E. M.

Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data sources: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.

Study selection: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

Data extraction: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.

Data synthesis: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).

Limitations: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.

Conclusion: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

Primary funding source: None. (PROSPERO: CRD42020163522).

Keywords 
Kidney Cholecalciferol Intention to Treat Analysis type 2 diabetes Randomized Controlled Trials as Topic

GLP1Agonists and SGLT2 Inhibitors Table

Author/s: 
Mold, J. W.

Based upon the following two meta-analyses:
1. Alexander JT, et al. The longer-term benefits and harms of glucagon-like peptide-1 receptor agonists: A Systematic review and meta-analysis. JGIM, 2021; 7(2): 415-43.
2. Alexander JT, et al. Longer-term benefits and risks of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes: A systematic review and meta-analysis. JGIM, 2021; 37(2): 439-44, plus Supplementary materials at https://doi.org/10.1007/s11606-021-07227-0.

Selection criteria for the RCTs was that the study period was at least 52 weeks in duration. I assume the average duration of the studies was at least 2 years. So, an absolute risk reduction of mortality of 0.5% would be per 2+ years.

Screening for Prediabetes and Type 2 Diabetes

Author/s: 
US Preventative Services task Force

IMPORTANCE An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5%
meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older
adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps
because of differences in the definition of prediabetes or the heterogeneity of prediabetes.
Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the
US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver
disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause
of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2
diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of
improving health outcomes.
OBJECTIVE To update its 2015 recommendation, the USPSTF commissioned a systematic
review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic,
nonpregnant adults and preventive interventions for those with prediabetes.
POPULATION Nonpregnant adults aged 35 to 70 years seen in primary care settings who have
overweight or obesity (defined as a body mass index 25 and 30, respectively) and no
symptoms of diabetes.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that screening for
prediabetes and type 2 diabetes and offering or referring patients with prediabetes to
effective preventive interventions has a moderate net benefit.
CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for prediabetes
and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians
should offer or refer patients with prediabetes to effective preventive interventions.
(B recommendation)

Screening for Gestational Diabetes: US Preventive Services Task Force Recommendation Statement

Author/s: 
US Preventive Services Task Force, Davidson, K. W., Barry, M. J., Mangione, C. M., Cabana, M., Caughey, A. B., Davis, E. M., Donahue, K. E., Doubeni, C. A., Kubik, M., Li, L., Ogedegbe, G., Pbert, L., Silberstein, M., Stevermer, J., Tseng, C., Wong, J. B.

Importance: Gestational diabetes is diabetes that develops during pregnancy. Prevalence of gestational diabetes in the US has been estimated at 5.8% to 9.2%, based on traditional diagnostic criteria, although it may be higher if more inclusive criteria are used. Pregnant persons with gestational diabetes are at increased risk for maternal and fetal complications, including preeclampsia, fetal macrosomia (which can cause shoulder dystocia and birth injury), and neonatal hypoglycemia. Gestational diabetes has also been associated with an increased risk of several long-term health outcomes in pregnant persons and intermediate outcomes in their offspring.

Objective: The USPSTF commissioned a systematic review to evaluate the accuracy, benefits, and harms of screening for gestational diabetes and the benefits and harms of treatment for the pregnant person and infant.

Population: Pregnant persons who have not been previously diagnosed with type 1 or type 2 diabetes.

Evidence assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit to screening for gestational diabetes at 24 weeks of gestation or after to improve maternal and fetal outcomes. The USPSTF concludes that the evidence on screening for gestational diabetes before 24 weeks of gestation is insufficient, and the balance of benefits and harms of screening cannot be determined.

Recommendation: The USPSTF recommends screening for gestational diabetes in asymptomatic pregnant persons at 24 weeks of gestation or after. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for gestational diabetes in asymptomatic pregnant persons before 24 weeks of gestation. (I statement).

Keywords 
Gestational Diabetes US Preventative Task Force Infancy Pregnancy Diagnostic Criteria

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2020 EXECUTIVE SUMMARY

Author/s: 
Garber, A.J., Handelsman, Y., Grunberger, G., Einhorn, D., Abrahamson, M.J., Barzilay, J.I., Blonde, L., Bush, M.A.

No abstract available.

Sex Difference in Effects of Low-Dose Aspirin on Prevention of Dementia in Patients With Type 2 Diabetes: A Long-term Follow-up Study of a Randomized Clinical Trial

Author/s: 
Matsumoto, C., Ogawa, H., Saito, Y., Okada S., Soejima, H., Sakuma, M., Masuda, I., Nakayama, M., Doi, N., Jinnouchi, H., Waki, M., Morimoto, T., JPAD Trial Investigators

OBJECTIVE:

To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women.

RESEARCH DESIGN AND METHODS:

This study is a follow-up cohort study of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which was a randomized, open-label, standard care-controlled trial examining the effects of low-dose aspirin on cardiovascular events. We followed up 2,536 Japanese patients with type 2 diabetes (T2D) enrolled in the JPAD trial from 2002 to 2017. The primary outcome of this post hoc analysis was the incidence of dementia, which was defined by the prescription of antidementia drugs or admission due to dementia.

RESULTS:

Among the originally enrolled patients, 2,121 (84%) retained their original allocation. During a median follow-up of 11.4 years, 128 patients developed dementia. The overall effect of low-dose aspirin on the prevention of dementia adjusted for age, sex, and other established risk factors was not significant (hazard ratio [HR] 0.82, 95% CI 0.58-1.16). However, a significant reduction was seen in the risk of dementia in women (HR 0.58, 95% CI 0.36-0.95), but not in men (HR 1.27, 95% CI 0.75-2.13) (P interaction = 0.03).

CONCLUSIONS:

Long-term use of low-dose aspirin may reduce the risk for dementia in women with T2D.

Keywords 
aspirin low-dose aspirin
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