OBJECTIVE

Variation in diabetes screening in clinical practice is poorly described. We examined the interplay of patient, provider, and clinic factors explaining variation in diabetes screening within an integrated health care system in the U.S.

RESEARCH DESIGN AND METHODS

We conducted a retrospective cohort study of primary care patients aged 18–64 years with two or more outpatient visits between 2010 and 2015 and no diagnosis of diabetes according to electronic health record (EHR) data. Hierarchical three-level models were used to evaluate multilevel variation in screening at the patient, provider, and clinic levels across 12 clinics. Diabetes screening was defined by a resulted gold standard screening test.

RESULTS

Of 56,818 patients, 70% completed diabetes screening with a nearly twofold variation across clinics (51–92%; P < 0.001). Of those meeting American Diabetes Association (ADA) (69%) and U.S. Preventive Services Task Force (USPSTF) (36%) screening criteria, three-quarters were screened with a nearly twofold variation across clinics (ADA 53–92%; USPSTF 49–93%). The yield of ADA and USPSTF screening was similar for diabetes (11% vs. 9%) and prediabetes (38% vs. 36%). Nearly 70% of patients not eligible for guideline-based screening were also tested. The USPSTF guideline missed more cases of diabetes (6% vs. 3%) and prediabetes (26% vs. 19%) than the ADA guideline. After adjustment for patient, provider, and clinic factors and accounting for clustering, twofold variation in screening by provider and clinic remained (median odds ratio 1.97; intraclass correlation 0.13).

CONCLUSIONS

Screening practices vary widely and are only partially explained by patient, provider, and clinic factors available in the EHR. Clinical decision support and system-level interventions are needed to optimize screening practices.

OBJECTIVE

We aimed to evaluate trends in bone mineral density (BMD) and the prevalence of osteoporosis/osteopenia in U.S. adults with prediabetes and normal glucose regulation (NGR) and further investigate the association among prediabetes, osteopenia/osteoporosis, and fracture.

RESEARCH DESIGN AND METHODS

We collected and analyzed data from the U.S. National Health and Nutrition Examination Surveys during the period from 2005 to 2014. Femoral neck and lumbar spine BMD data were available for 5,310 adults with prediabetes and 5,162 adults with NGR >40 years old.

RESULTS

A shift was observed toward a lower BMD and a higher prevalence of osteopenia/osteoporosis at the femoral neck and lumbar spine in U.S. adults >40 years old with prediabetes since 2005, especially in men <60 and women ≥60 years old. A shift toward a higher prevalence of osteopenia/osteoporosis at the femoral neck was also observed in adults >40 years old with NGR. Moreover, prediabetes was associated with a higher prevalence of hip fracture, although participants with prediabetes had higher BMD and a lower prevalence of osteopenia/osteoporosis at the femoral neck.

CONCLUSIONS

There was a declining trend in BMD from 2005 to 2014 in U.S. adults >40 years old with prediabetes and NGR, and this trend was more significant in men <60 years old. Populations with prediabetes may be exposed to relatively higher BMD but a higher prevalence of fracture.

OBJECTIVE

We investigated the association between changes in weight status from childhood through adulthood and subsequent type 2 diabetes risks and whether educational attainment, smoking, and leisure time physical activity (LTPA) modify this association.

RESEARCH DESIGN AND METHODS

Using data from 10 Danish and Finnish cohorts including 25,283 individuals, childhood BMI at 7 and 12 years was categorized as normal or high using age- and sex-specific cutoffs (<85th or ≥85th percentile). Adult BMI (20–71 years) was categorized as nonobese or obese (<30.0 or ≥30.0 kg/m², respectively). Associations between BMI patterns and type 2 diabetes (989 women and 1,370 men) were analyzed using Cox proportional hazards regressions and meta-analysis techniques.

RESULTS

Compared with individuals with a normal BMI at 7 years and without adult obesity, those with a high BMI at 7 years and adult obesity had higher type 2 diabetes risks (hazard ratio [HR]_girls 5.04 [95% CI 3.92–6.48]; HR_boys 3.78 [95% CI 2.68–5.33]). Individuals with a high BMI at 7 years but without adult obesity did not have a higher risk (HR_girls 0.74 [95% CI 0.52–1.06]; HR_boys 0.93 [95% CI 0.65–1.33]). Education, smoking, and LTPA were associated with diabetes risks but did not modify or confound the associations with BMI changes. Results for 12 years of age were similar.

CONCLUSIONS

A high BMI in childhood was associated with higher type 2 diabetes risks only if individuals also had obesity in adulthood. These associations were not influenced by educational and lifestyle factors, indicating that BMI is similarly related to the risk across all levels of these factors.

OBJECTIVE

The effect of early-life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis.

RESEARCH DESIGN AND METHODS

All singleton children (n = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings.

RESULTS

Type 1 diabetes developed in 1,297 children during the follow-up (median 4.0 years [range 0–8.3]). Prescribed antibiotics in the 1st year of life (23.8%) were associated with an increased risk of type 1 diabetes (adjusted hazard ratio [HR] 1.19 [95% CI 1.05–1.36]), with larger effect estimates among children delivered by cesarean section (P for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00–1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations.

CONCLUSIONS

Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10 years, most prominently in children delivered by cesarean section.

OBJECTIVE

To determine the incidence of and factors associated with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² in people with diabetes.

RESEARCH DESIGN AND METHODS

We identified people with diabetes in the EXamining ouTcomEs in chroNic Disease in the 45 and Up Study (EXTEND45), a population-based cohort study (2006–2014) that linked the Sax Institute’s 45 and Up Study cohort to community laboratory and administrative data in New South Wales, Australia. The study outcome was the first eGFR measurement <60 mL/min/1.73 m² recorded during the follow-up period. Participants with eGFR < 60 mL/min/1.73 m² at baseline were excluded. We used Poisson regression to estimate the incidence of eGFR <60 mL/min/1.73 m² and multivariable Cox regression to examine factors associated with the study outcome.

RESULTS

Of 9,313 participants with diabetes, 2,106 (22.6%) developed incident eGFR <60 mL/min/1.73 m² over a median follow-up time of 5.7 years (interquartile range, 3.0–5.9 years). The eGFR <60 mL/min/1.73 m² incidence rate per 100 person-years was 6.0 (95% CI 5.7–6.3) overall, 1.5 (1.3–1.9) in participants aged 45–54 years, 3.7 (3.4–4.0) for 55–64 year olds, 7.6 (7.1–8.1) for 65–74 year olds, 15.0 (13.0–16.0) for 75–84 year olds, and 26.0 (22.0–32.0) for those aged 85 years and over. In a fully adjusted multivariable model incidence was independently associated with age (hazard ratio 1.23 per 5-year increase; 95% CI 1.19–1.26), geography (outer regional and remote versus major city: 1.36; 1.17–1.58), obesity (obese class III versus normal: 1.44; 1.16–1.80), and the presence of hypertension (1.52; 1.33–1.73), coronary heart disease (1.13; 1.02–1.24), cancer (1.30; 1.14–1.50), and depression/anxiety (1.14; 1.01–1.27).

CONCLUSIONS

In participants with diabetes, the incidence of an eGFR <60 mL/min/1.73 m² was high. Older age, remoteness of residence, and the presence of various comorbid conditions were associated with higher incidence.

OBJECTIVE

The prevalence of type 2 diabetes is increasing among adults under age 45. Onset of type 2 diabetes at a younger age increases an individual’s risk for diabetes-related complications. Given the lasting benefits conferred by early glycemic control, we compared glycemic control and initial care between adults with younger onset (21–44 years) and mid-age onset (45–64 years) of type 2 diabetes.

RESEARCH DESIGN AND METHODS

Using data from a large, integrated health care system, we identified 32,137 adults (aged 21–64 years) with incident diabetes (first HbA_1c ≥6.5% [≥48 mmol/mol]). We excluded anyone with evidence of prior type 2 diabetes, gestational diabetes mellitus, or type 1 diabetes. We used generalized linear mixed models, adjusting for demographic and clinical variables, to examine differences in glycemic control and care at 1 year.

RESULTS

Of identified individuals, 26.4% had younger-onset and 73.6% had mid-age–onset type 2 diabetes. Adults with younger onset had higher initial mean HbA_1c values (8.9% [74 mmol/mol]) than adults with onset in mid-age (8.4% [68 mmol/mol]) (P < 0.0001) and lower odds of achieving an HbA_1c <7% (<53 mmol/mol) 1 year after the diagnosis (adjusted odds ratio [aOR] 0.70 [95% CI 0.66–0.74]), even after accounting for HbA_1c at diagnosis. Adults with younger onset had lower odds of in-person primary care contact (aOR 0.82 [95% CI 0.76–0.89]) than those with onset during mid-age, but they did not differ in telephone contact (1.05 [0.99–1.10]). Adults with younger onset had higher odds of starting metformin (aOR 1.20 [95% CI 1.12–1.29]) but lower odds of adhering to that medication (0.74 [0.69–0.80]).

CONCLUSIONS

Adults with onset of type 2 diabetes at a younger age were less likely to achieve glycemic control at 1 year following diagnosis, suggesting the need for tailored care approaches to improve outcomes for this high-risk patient population.

OBJECTIVE

No study has reported global disability burden estimates for individual diabetes-related lower-extremity complications (DRLECs). The Global Burden of Disease (GBD) study presents a robust opportunity to address this gap.

RESEARCH DESIGN AND METHODS

GBD 2016 data, including prevalence and years lived with disability (YLDs), for the DRLECs of diabetic neuropathy, foot ulcer, and amputation with and without prosthesis were used. The GBD estimated prevalence using data from systematic reviews and DisMod-MR 2.1, a Bayesian meta-regression tool. YLDs were estimated as the product of prevalence estimates and disability weights for each DRLEC. We reported global and sex-, age-, region-, and country-specific estimates for each DRLEC for 1990 and 2016.

RESULTS

In 2016, an estimated 131 million people (1.8% of the global population) had DRLECs. An estimated 16.8 million YLDs (2.1% global YLDs) were caused by DRLECs, including 12.9 million (95% uncertainty interval 8.30–18.8) from neuropathy only, 2.5 million (1.7–3.6) from foot ulcers, 1.1 million (0.7–1.4) from amputation without prosthesis, and 0.4 million (0.3–0.5) from amputation with prosthesis. Age-standardized YLD rates of all DRLECs increased by between 14.6% and 31.0% from 1990 estimates. Male-to-female YLD ratios ranged from 0.96 for neuropathy only to 1.93 for foot ulcers. The 50- to 69-year-old age-group accounted for 47.8% of all YLDs from DRLECs.

CONCLUSIONS

These first-ever global estimates suggest that DRLECs are a large and growing contributor to the disability burden worldwide and disproportionately affect males and middle- to older-aged populations. These findings should facilitate policy makers worldwide to target strategies at populations disproportionately affected by DRLECs.

OBJECTIVE

Daily foot self-inspection may permit earlier detection and treatment of a foot lesion, reducing the risk of infection and lower-limb amputation (LLA). Though race and ethnicity are strongly associated with LLA risk, with higher risk seen in African Americans (AA), American Indians/Alaska Natives (AI/AN), and Native Hawaiians/Pacific Islanders (NH/PI), associations between foot self-inspection and racial and ethnic groups are inconsistent. We aimed to assess differences in foot self-inspection among people with diabetes by race/ethnicity.

RESEARCH DESIGN AND METHODS

Using national, cross-sectional data from the 2015–2017 Behavioral Risk Factor Surveillance System surveys and including 88,424 individuals with diabetes, we estimated prevalence ratios (PRs) and associated 95% CIs of daily foot checking for sores or irritation by racial and ethnic groups using log-binomial linear regression models, after accounting for survey weights.

RESULTS

Compared with whites (who had a weighted prevalence [P] of daily foot self-inspection of 57%), AA (P 67%, PR 1.18 [95% CI 1.14, 1.23]), AI/AN (P 66%, PR 1.15 [95% CI 1.07, 1.25]), and NH/PI (P 71%, PR 1.25 [95% CI 1.03, 1.52]) had higher prevalences of daily foot self-inspection. The prevalence of daily foot inspection was significantly lower among Asians (P 35%, PR 0.62 [95% CI 0.48, 0.81]) and Hispanics (P 53%, PR 0.93 [95% CI 0.88, 0.99]) compared with whites. Associations did not vary importantly by insulin use, years since diabetes diagnosis, or having received diabetes self-management education.

CONCLUSIONS

The higher frequency of foot self-inspection in racial and ethnic groups at elevated risk of diabetes-related LLA is not sufficient to eliminate LLA disparities; additional interventions are needed to achieve this aim.

Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania (n = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients (n = 153) using targeted high-throughput sequencing of >300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0–12 months), followed by those diagnosed at ages >1–18 years (40.3%) and >18–25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in >50% of eligible candidates, with C-peptide >252 pmol/L emerging as the best prognostic factor.

MG53 is a member of the TRIM protein family that is predominantly expressed in striated muscles and participates in cell membrane repair. Controversy exists regarding MG53’s role in insulin signaling and manifestation of diabetes. We generated db/db mice with either whole-body ablation or sustained elevation of MG53 in the bloodstream in order to evaluate the physiological function of MG53 in diabetes. To quantify the amount of MG53 protein in circulation, we developed a monoclonal antibody against MG53 with high specificity. Western blot using this antibody revealed lower or no change of serum MG53 levels in db/db mice or patients with diabetes compared with control subjects. Neither whole-body ablation of MG53 nor sustained elevation of MG53 in circulation altered insulin signaling and glucose handling in db/db mice. Instead, mice with ablation of MG53 were more susceptible to streptozotocin-induced dysfunctional handling of glucose compared with the wild-type littermates. Alkaline-induced corneal injury demonstrated delayed healing in db/db mice, which was restored by topical administration of recombinant human (rh)MG53. Daily intravenous administration of rhMG53 in rats at concentrations up to 10 mg/kg did not produce adverse effects on glucose handling. These findings challenge the hypothetical function of MG53 as a causative factor for the development of diabetes. Our data suggest that rhMG53 is a potentially safe and effective biologic to treat diabetic oculopathy in rodents.

Impaired baroreflex sensitivity (BRS) predicts cardiovascular mortality and is prevalent in long-term diabetes. We determined spontaneous BRS in patients with recent-onset diabetes and its temporal sequence over 5 years by recording beat-to-beat blood pressure and R-R intervals over 10 min. Four time domain and four frequency domain BRS indices were computed in participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 206/381) and age-matched glucose-tolerant control subjects (control 1/control 2: n = 65/83) and subsets of consecutive participants with type 1/type 2 diabetes who reached the 5-year follow-up (n = 84/137). Insulin sensitivity (M-value) was determined using a hyperinsulinemic-euglycemic clamp. After appropriate adjustment, three frequency domain BRS indices were reduced in type 2 diabetes compared with control 2 and were positively associated with the M-value and inversely associated with fasting glucose and HbA_1c (P < 0.05), whereas BRS was preserved in type 1 diabetes. After 5 years, a decrease in one and four BRS indices was observed in patients with type 1 and type 2 diabetes, respectively (P < 0.05), which was explained by the physiologic age-dependent decline. Unlike patients with well-controlled recent-onset type 1 diabetes, those with type 2 diabetes show early baroreflex dysfunction, likely due to insulin resistance and hyperglycemia, albeit without progression over 5 years.

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated that intensive glucose control reduced the risk of developing diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). We evaluated multiple risk factors and phenotypes associated with DPN and CAN in this large, well-characterized cohort of participants with type 1 diabetes, followed for >23 years. DPN was defined by symptoms, signs, and nerve conduction study abnormalities in ≥2 nerves; CAN was assessed using standardized cardiovascular reflex tests. Generalized estimating equation models assessed the association of DPN and CAN with individual risk factors measured repeatedly. During DCCT/EDIC, 33% of participants developed DPN and 44% CAN. Higher mean HbA_1c was the most significant risk factor for DPN, followed by older age, longer duration, greater height, macroalbuminuria, higher mean pulse rate, β-blocker use, and sustained albuminuria. The most significant risk factor for CAN was older age, followed by higher mean HbA_1c, sustained albuminuria, longer duration of type 1 diabetes, higher mean pulse rate, higher mean systolic blood pressure, β-blocker use, estimated glomerular filtration rate <60 mL/min/1.73 m², higher most recent pulse rate, and cigarette smoking. These findings identify risk factors and phenotypes of participants with diabetic neuropathy that can be used in the design of new interventional trials and for personalized approaches to neuropathy prevention.

As an alternative to lifelong insulin supplementation, potentiation of immune tolerance in patients with type 1 diabetes could prevent the autoimmune destruction of pancreatic islet β-cells. This study was aimed to assess whether the G3c monoclonal antibody (mAb), which triggers the glucocorticoid-induced TNFR-related (Gitr) costimulatory receptor, promotes the expansion of regulatory T cells (Tregs) in SV129 (wild-type) and diabetic-prone NOD mice. The delivery of the G3c mAb via G3C hybridoma cells enveloped in alginate-based microcapsules (G3C/cps) for 3 weeks induced Foxp3⁺ Treg-cell expansion in the spleen of wild-type mice but not in Gitr^–/– mice. G3C/cps also induced the expansion of nonconventional Cd4⁺Cd25^–/lowFoxp3^lowGitr^int/high (GITR single-positive [sp]) Tregs. Both Cd4⁺Cd25⁺Gitr^highFoxp3⁺ and GITRsp Tregs (including also antigen-specific cells) were expanded in the spleen and pancreas of G3C/cps-treated NOD mice, and the number of intact islets was higher in G3C/cps-treated than in empty cps-treated and untreated animals. Consequently, all but two G3C/cps-treated mice did not develop diabetes and all but one survived until the end of the 24-week study. In conclusion, long-term Gitr triggering induces Treg expansion, thereby delaying/preventing diabetes development in NOD mice. This therapeutic approach may have promising clinical potential for the treatment of inflammatory and autoimmune diseases.

Abnormal interactions between misfolded mutant and wild-type (WT) proinsulin (PI) in the endoplasmic reticulum (ER) drive the molecular pathogenesis of mutant INS gene–induced diabetes of youth (MIDY). How these abnormal interactions are initiated remains unknown. Normally, PI-WT dimerizes in the ER. Here, we suggest that the normal PI-PI contact surface, involving the B-chain, contributes to dominant-negative effects of misfolded MIDY mutants. Specifically, we find that PI B-chain tyrosine-16 (Tyr-B16), which is a key residue in normal PI dimerization, helps confer dominant-negative behavior of MIDY mutant PI-C(A7)Y. Substitutions of Tyr-B16 with either Ala, Asp, or Pro in PI-C(A7)Y decrease the abnormal interactions between the MIDY mutant and PI-WT, rescuing PI-WT export, limiting ER stress, and increasing insulin production in β-cells and human islets. This study reveals the first evidence indicating that noncovalent PI-PI contact initiates dominant-negative behavior of misfolded PI, pointing to a novel therapeutic target to enhance PI-WT export and increase insulin production.

Vitamin D deficiency has been associated with increased incidence of diabetes, both in humans and in animal models. In addition, an association between vitamin D receptor (VDR) gene polymorphisms and diabetes has also been described. However, the involvement of VDR in the development of diabetes, specifically in pancreatic β-cells, has not been elucidated yet. Here, we aimed to study the role of VDR in β-cells in the pathophysiology of diabetes. Our results indicate that Vdr expression was modulated by glucose in healthy islets and decreased in islets from both type 1 diabetes and type 2 diabetes mouse models. In addition, transgenic mice overexpressing VDR in β-cells were protected against streptozotocin-induced diabetes and presented a preserved β-cell mass and a reduction in islet inflammation. Altogether, these results suggest that sustained VDR levels in β-cells may preserve β-cell mass and β-cell function and protect against diabetes.

Insulin resistance is an underappreciated facet of type 1 diabetes that occurs with remarkable consistency and considerable magnitude. Although therapeutic innovations are continuing to normalize dysglycemia, a sizable body of data suggests a second metabolic abnormality—iatrogenic hyperinsulinemia—principally drives insulin resistance and its consequences in this population and has not been addressed. We review this evidence to show that injecting insulin into the peripheral circulation bypasses first-pass hepatic insulin clearance, which leads to the unintended metabolic consequence of whole-body insulin resistance. We propose restructuring insulin therapy to restore the physiological insulin balance between the hepatic portal and peripheral circulations and thereby avoid the complications of life-long insulin resistance. As technology rapidly advances and our ability to ensure euglycemia improves, iatrogenic insulin resistance will become the final barrier to overcome to restore normal physiology, health, and life in type 1 diabetes.

Impaired insulin secretion from the pancreatic β-cells is central in the pathogenesis of type 2 diabetes (T2D), and microRNAs (miRNAs) are fundamental regulatory factors in this process. Differential expression of miRNAs contributes to β-cell adaptation to compensate for increased insulin resistance, but deregulation of miRNA expression can also directly cause β-cell impairment during the development of T2D. miRNAs are small noncoding RNAs that posttranscriptionally reduce gene expression through translational inhibition or mRNA destabilization. The nature of miRNA targeting implies the presence of complex and large miRNA–mRNA regulatory networks in every cell, including the insulin-secreting β-cell. Here we exemplify one such network using our own data on differential miRNA expression in the islets of T2D Goto-Kakizaki rat model. Several biological processes are influenced by multiple miRNAs in the β-cell, but so far most studies have focused on dissecting the mechanism of action of individual miRNAs. In this Perspective we present key islet miRNA families involved in T2D pathogenesis including miR-200, miR-7, miR-184, miR-212/miR-132, and miR-130a/b/miR-152. Finally, we highlight four challenges and opportunities within islet miRNA research, ending with a discussion on how miRNAs can be utilized as therapeutic targets contributing to personalized T2D treatment strategies.

PURPOSE

We aimed to evaluate the efficacy and safety of use of the Fasting Algorithm for Singaporeans with Type 2 Diabetes (FAST) during Ramadan.

METHODS

We performed a prospective, multicenter, randomized controlled trial. The inclusion criteria were age ≥21 years, baseline glycated hemoglobin (HbA_1c) level ≤9.5%, and intention to fast for ≥10 days during Ramadan. Exclusion criteria included baseline estimated glomerular filtration rate <30 mL/min, diabetes-related hospitalization, and short-term corticosteroid therapy. Participants were randomized to intervention (use of FAST) or control (usual care without FAST) groups. Efficacy outcomes were HbA_1c level and fasting blood glucose and postprandial glucose changes, and the safety outcome was incidence of major or minor hypoglycemia during the Ramadan period. Glycemic variability and diabetes distress were also investigated. Linear mixed models were constructed to assess changes.

RESULTS

A total of 97 participants were randomized (intervention: n = 46, control: n = 51). The HbA_1c improvement during Ramadan was 4 times greater in the intervention group (–0.4%) than in the control group (–0.1%) (P = .049). The mean fasting blood glucose level decreased in the intervention group (–3.6 mg/dL) and increased in the control group (+20.9 mg/dL) (P = .034). The mean postprandial glucose level showed greater improvement in the intervention group (–16.4 mg/dL) compared to the control group (–2.3 mg/dL). There were more minor hypoglycemic events based on self-monitered blood glucose readings in the control group (intervention: 4, control: 6; P = .744). Glycemic variability was not significantly different between the 2 groups (P = .284). No between-group differences in diabetes distress were observed (P = .479).

CONCLUSIONS

Our findings emphasize the importance of efficacious, safe, and culturally tailored epistemic tools for diabetes management.

Background and objectives

Large, randomized, controlled trials targeting higher hemoglobin level with erythropoiesis-stimulating agents for Western patients with CKD showed harm. However, the effect of anemia correction using erythropoiesis-stimulating agents may differ between CKD subpopulations. The Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease study, a multicenter, randomized, open-label, parallel-group study, aimed to examine the effect of targeting hemoglobin levels of 11–13 g/dl using darbepoetin alfa with reference to a low-hemoglobin target of 9–11 g/dl on kidney outcome in patients with advanced CKD without diabetes in Japan.

Design, setting, participants, & measurements

We enrolled 491 patients with CKD without diabetes, and an eGFR of 8–20 ml/min per 1.73 m². Of these 491 patients, 239 and 240 were ultimately assigned to the high- and low-hemoglobin groups, respectively (12 patients were excluded). The primary outcome was a kidney composite end point (starting maintenance dialysis, kidney transplantation, eGFR≤6 ml/min per 1.73 m², and 50% reduction in eGFR).

Results

Mean hemoglobin levels were 11.2±1.1 and 10.0±0.9 g/dl in the high- and low-hemoglobin groups, respectively, during the mean study period of 73.5±29.7 weeks. The kidney composite end point occurred in 105 (44%) and 116 (48%) patients in the high- and low-hemoglobin groups, respectively (log-rank test; P=0.32). The adjusted Cox proportional hazards model showed that the hazard ratio for the high- versus low-hemoglobin group was 0.78 (95% confidence interval, 0.60 to 1.03; P=0.08). Cardiovascular events occurred in 19 (8%) and 16 (7%) patients in each group, respectively, with no significant between-group difference (log-rank test; P=0.66).

Conclusions

Targeting a higher hemoglobin level (11–13 g/dl) with darbepoetin alfa did not improve kidney outcome compared with targeting a lower hemoglobin level (9–11 g/dl) in patients with advanced CKD without diabetes.

Clinical Trial registry name and registration number

Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease (PREDICT), NCT01581073.

Background:

First Nations people in Ontario have an increased prevalence of diabetes compared to other people in the province. This study examined use of health care services by First Nations people with diabetes and other people with diabetes in Ontario.

Methods:

Using linked health administrative databases, we identified all people in Ontario with diabetes as of Apr. 1, 2014. We identified First Nations people using the Indian Register. We looked at outcomes from Apr. 1, 2014, to Mar. 31, 2015. We determined the proportion of people with a regular family physician and their continuity of care with that physician. We also examined visits with specialists for diabetes care, hospital admissions for ambulatory-care–sensitive conditions, and emergency department visits for hypo- or hyperglycemia.

Results:

There were 1 380 529 people diagnosed with diabetes in Ontario as of Apr. 1, 2014, of whom 22 952 (1.7%) were First Nations people. First Nations people were less likely to have a regular family physician (85.3% v. 97.7%) and had lower continuity of care with that physician (mean score for continuity of care 74.6 v. 77.7) than other people in Ontario. They were also less likely to see specialists. First Nations people were more likely to be admitted to hospital for ambulatory-care–sensitive conditions (2.4% v. 1.2%) and to have an emergency department visit for hypo- or hyperglycemia (1.5% v. 0.8%). Disparities were particularly marked for those living in First Nations communities.

Interpretation:

First Nations people with diabetes in Ontario had poorer access to and use of primary care than other people with diabetes in the province. These findings may help explain continued disparities in the rates of complications related to diabetes.

Background:

In Canada, First Nations populations experience a higher incidence of diabetes and diabetes-related complications than other people. Given the paucity of information on use of preventive eye examinations and the need for interventional care for severe retinopathy among First Nations people, we carried out a population-based study to compare rates of eye examinations and interventional therapies to treat vision-threatening stages of diabetic retinopathy among First Nations people and other people with diabetes in Ontario.

Methods:

In collaboration with the Chiefs of Ontario, we carried out a population-based study to identify cohorts of First Nations people and other people with diabetes in Ontario from 1995/96 to 2014/15. We used linked health administrative databases to evaluate rates of eye examination (2005/06–2014/15) and severe diabetic retinopathy treatment and compared them between the 2 populations, and between First Nations people living in and outside of First Nations communities.

Results:

We identified 23 013 First Nations people and 1 364 222 other people diagnosed with diabetes from 1995/96 to 2014/15, of whom 49.8% (95% confidence interval [CI] 48.9%–50.7%) and 53.8% (95% CI 53.7%–54.0%), respectively, received an eye examination in 2014/15. Eye examination rates were similar for First Nations people regardless of whether they lived in or outside a First Nations community. First Nations people developed severe diabetic retinopathy at a faster rate than other people (hazard ratio 1.19, 95% CI 1.02–1.38). The gap between First Nations people and other people in the proportion requiring therapy for severe diabetic retinopathy was especially prominent among younger people. There were no significant differences in rates of diabetic retinopathy treatment in First Nations people stratified by place of residence.

Interpretation:

Eye examination rates remain suboptimal among people with diabetes in Ontario and were lower among First Nations people. This is particularly concerning in light of our other findings showing an increased risk of requiring treatment for advanced diabetic retinopathy and the accelerated rate of diabetic retinopathy progression among First Nations people with diabetes.

The aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population.We conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro–B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A_1c [Hb A_1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016–2017; age 71–94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adults with and without diabetes after adjusting for traditional risk factors.In total, 33.5% of participants had PN (37.3% with diabetes and 31.9% without diabetes). There was an independent association of hs-cTnT with PN regardless of diabetes status (diabetes T3 vs. T1: odds ratio [OR], 2.15 [95% CI, 1.44–3.22]; no diabetes: OR, 2.31 [95%CI, 1.76–3.03]; P = 0.72 for interaction). Among participants without diabetes, there were also significant associations of NT-proBNP (OR, 1.40 [95% CI, 1.08–1.81]) and urine albumin-to-creatinine ratio (OR, 1.55 [95% CI, 1.22–1.97]) with PN. Associations of hyperglycemia biomarkers including Hb A_1c (OR, 1.76 [95% CI, 1.22–2.54]), fructosamine (OR, 1.71 [95% CI, 1.19–2.46]), and glycated albumin (OR, 1.45 [95% CI, 1.03–2.03]) with PN were significant only among participants with diabetes.Overall, hs-cTnT appears to be a global marker of end organ damage, including PN. Laboratory biomarkers may be able to help us identify those individuals with PN.

Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain.We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk.We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR.We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age.

Although they are usually not considered to be diabetes complications, musculoskeletal disorders (MSKDs) are common in individuals with type 1 or type 2 diabetes and can strongly interfere with daily diabetes care, especially in people using diabetes technologies. The authors of this retrospective study in a population of 140 patients with type 1 diabetes report the distribution of subtypes of MSKDs and speculate about the mechanisms involved. The authors emphasize the need for multidisciplinary care involving not only the diabetes care team but also orthopedic surgeons. This report should lead to large, prospective studies to increase knowledge about these under-studied complications.

This study was an analysis of a national sample of U.S. medical office visits from 2014 to 2016, a period when evidence of effectiveness was emerging for a variety of beneficial type 2 diabetes agents with regard to potential reduction in diabetes comorbidities. Ideal therapy was defined as an American Diabetes Association–identified beneficial agent plus metformin. The associations between atherosclerotic cardiovascular disease or obesity and use of these agents were explored.

Structured diabetes education (SDE) is an evidence-based intervention that supports self-management in people with type 2 diabetes. In the United Kingdom, health care providers working in primary care settings are responsible for referring people with type 2 diabetes to SDE programs. However, national audits record a high percentage of nonattenders. We explored the personal experience of living with type 2 diabetes that led to individuals declining invitations to attend SDE programs. The themes suggested that emotional, cognitive, and social issues related to diagnosis and living with diabetes may be responsible for declining to attend SDE and that these factors may be masked by explanations of practical barriers. A person-centered approach to understanding the personal meaning of being diagnosed and living with type 2 diabetes may help to identify individuals’ psychosocial barriers to attending SDE.

People with type 1 diabetes may receive a significant portion of their care from primary care providers (PCPs). To understand the involvement of PCPs in delivering type 1 diabetes care, we performed surveys in California and Florida, two of the most populous and diverse states in the United States. PCPs fill insulin prescriptions but report low confidence in providing type 1 diabetes care and difficulty accessing specialty referrals to endocrinologists.

Adolescents with type 1 diabetes face self-management challenges that make it difficult for them to achieve good glycemic control. In our population of adolescents with poorly controlled type 1 diabetes, the use of continuous glucose monitoring (CGM) improved patients’ glycemic time in range (TIR) and identified hypoglycemia more frequently than with intermittent self-monitoring of blood glucose throughout a 4-week interval. However, the adolescents were unable to synthesize this information to problem-solve or reduce the frequency of hypoglycemic events. Setting SMART (specific, measurable, achievable, relevant, and time-bound) diabetes management goals and providing intensive diabetes education and support could increase adolescents’ TIR and prevent hypoglycemia.

This research shows how different populations of people share most of the genetic susceptibilities to developing type 2 diabetes but do have some different genetic variations that can make them more or less susceptible to developing the condition.

A device that carries hot water down a tube into the gut may help manage diabetes by killing overgrown gut cells that release hormones key to metabolising food

According to many observations, certain virus infections may play a part in the autoimmune attack that leads to type 1 diabetes. Researchers have now produced a vaccine for these viruses in the hope that it could provide protection against the disease.