ContextHigher rates of microvascular complications have been reported for minorities. Disparate access to quality health care is a common explanation for ethnic disparities in diabetic complication rates in the US population. Examining an ethnically diverse population with uniform health care coverage may be useful.Objective To assess ethnic disparities in the incidence of diabetic complications within a nonprofit prepaid health care organization.

In the coming decades, the population of older adults with type 2 diabetes mellitus is expected to grow substantially. Understanding the clinical course of diabetes in this population is critical for establishing evidence-based clinical practice recommendations, identifying research priorities, allocating resources, and setting health care policies.OBJECTIVE To contrast the rates of diabetes complications and mortality across age and diabetes duration categories. This cohort study (2004This cohort study ( -2010 included 72 310 older (Ն60 years) patients with type 2 diabetes enrolled in a large, integrated health care delivery system. Incidence densities (events per 1000 person-years) were calculated for each age category (60-69, 70-79, and Ն80 years) and duration of diabetes (shorter [0-9 years] vs longer [Ն10 years]). DESIGN, SETTING, AND PARTICIPANTS MAIN OUTCOMES AND MEASURESIncident acute hyperglycemic events, acute hypoglycemic events (hypoglycemia), microvascular complications (end-stage renal disease, peripheral vascular disease, lower limb amputation, and diabetic eye disease), cardiovascular complications (coronary artery disease, cerebrovascular disease, and congestive heart failure), and all-cause mortality.RESULTS Among older adults with diabetes of short duration, cardiovascular complications followed by hypoglycemia were the most common nonfatal complications. For example, among individuals aged 70 to79 years with a short duration of diabetes, coronary artery disease and hypoglycemia rates were higher (11.47 per 1000 person-years and 5.03 per 1000 person-years, respectively) compared with end-stage renal disease (2.60 per 1000 person-years), lower limb amputation (1.28 per 1000 person-years), and acute hyperglycemic events (0.82 per 1000 person-years). We observed a similar pattern among patients in the same age group with a long duration of diabetes, with some of the highest incidence rates in coronary artery disease and hypoglycemia (18.98 per 1000 person-years and 15.88 per 1000 person-years, respectively) compared with end-stage renal disease (7.64 per 1000 person-years), lower limb amputation (4.26 per 1000 person-years), and acute hyperglycemic events (1.76 per 1000 person-years). For a given age group, the rates of each outcome, particularly hypoglycemia and microvascular complications, increased dramatically with longer duration of the disease. However, for a given duration of diabetes, rates of hypoglycemia, cardiovascular complications, and mortality increased steeply with advancing age, and rates of microvascular complications remained stable or declined.CONCLUSIONS AND RELEVANCE Duration of diabetes and advancing age independently predict diabetes morbidity and mortality rates. As long-term survivorship with diabetes increases and as the population ages, more research and public health efforts to reduce hypoglycemia will be needed to complement ongoing efforts to reduce cardiovascular and microvascular complications.

The authors investigated use of the internet-based patient portal, kp.org, among a well-characterized population of adults with diabetes in Northern California. Among 14,102 diverse patients, 5671 (40%) requested a password for the patient portal. Of these, 4311 (76%) activated their accounts, and 3922 (69%), logged on to the patient portal one or more times; 2990 (53%) participants viewed laboratory results, 2132 (38%) requested medication refills, 2093 (37%) sent email messages, and 835 (15%) made medical appointments. After adjustment for age, gender, race/ethnicity, immigration status, educational attainment, and employment status, compared to non-Hispanic Caucasians, African-Americans and Latinos had higher odds of never logging on (OR 2.6 (2.3 to 2.9); OR 2.3 (1.9 to 2.6)), as did those without an educational degree (OR compared to college graduates, 2.3 (1.9 to 2.7)). Those most at risk for poor diabetes outcomes may fall further behind as health systems increasingly rely on the internet and limit current modes of access and communication.

Traditionally viewed as an autodigestive pathway, autophagy also facilitates cellular secretion; however, the mechanisms underlying these processes remain unclear. Here, we demonstrate that components of the autophagy machinery specify secretion within extracellular vesicles (EVs). Using a proximity-dependent biotinylation proteomics strategy, we identify 200 putative targets of LC3-dependent secretion. This secretome consists of a highly interconnected network enriched in RNA-binding proteins (RBPs) and EV cargoes. Proteomic and RNA-profiling of EVs identifies diverse RBPs and small non-coding RNAs requiring the LC3-conjugation machinery for packaging and secretion. Focusing on two RBPs, heterogeneous nuclear ribonucleoprotein K (HNRNPK) and scaffold-attachment factor B (SAFB), we demonstrate these proteins interact with LC3 and are secreted within EVs enriched with lipidated LC3. Furthermore, their secretion requires the LC3-conjugation machinery, neutral sphingomyelinase 2 (nSMase2), and LC3-dependent recruitment of Factor-associated with nSMase2 activity (FAN). Hence, the LC3-conjugation pathway controls EV cargo loading and secretion.

Among patients with newly diagnosed diabetes and 10 years of survival, HbA levels ≥6.5% (≥48 mmol/mol) for the 1st year after diagnosis were associated with worse outcomes. Immediate, intensive treatment for newly diagnosed patients may be necessary to avoid irremediable long-term risk for diabetic complications and mortality.

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These results confirm previous evidence that poor glycemic control may be associated with an increased risk of heart failure among adult patients with diabetes.

OBJECTIVETo identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients.RESEARCH DESIGN AND METHODSWe conducted a retrospective cohort study (2004–2008) of 71,092 patients with type 2 diabetes, aged ≥60 years, enrolled in Kaiser Permanente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality).RESULTSThe cohort (aged 71.0 ± 7.4 years [means ± SD]) had a mean A1C of 7.0 ± 1.2%. The risk of any nonfatal complication rose monotonically for levels of A1C >6.0% (e.g., adjusted hazard ratio 1.09 [95% CI 1.02–1.16] for A1C 6.0–6.9% and 1.86 [1.63–2.13] for A1C ≥11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C <6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0% (e.g., 0.83 [0.76–0.90] for A1C 7.0–7.9%) and higher at A1C ≥11.0% (1.31 [1.09–1.57]). Risk of any end point (complication or death) became significantly higher at A1C ≥8.0%. Patterns generally were consistent across age-groups (60–69, 70–79, and ≥80 years).CONCLUSIONSObserved relationships between A1C and combined end points support setting a target of A1C <8.0% for older patients, with the caution that A1Cs <6.0% were associated with increased mortality risk. Additional research is needed to evaluate the low A1C–mortality relationship, as well as protocols for individualizing diabetes care.