Diabetes frequently develops in patients with chronic pancreatitis. We examined the alterations in the glucagon response to hypoglycemia and to oral glucose administration in patients with diabetes due to chronic pancreatitis.

Ten patients with diabetes secondary to chronic pancreatitis were compared with 13 patients with type 2 diabetes and 10 healthy control subjects. A stepwise hypoglycemic clamp and an oral glucose tolerance test (OGTT) were performed.

Glucose levels during the OGTT were higher in patients with diabetes and chronic pancreatitis and lower in control subjects (P < 0.0001). Insulin and C-peptide levels were reduced, and the glucose-induced suppression of glucagon was impaired in both groups with diabetes (all P < 0.0001 vs. control subjects). During hypoglycemia, glucagon concentrations were reduced in patients with chronic pancreatitis and with type 2 diabetes (P < 0.05). The increase in glucagon during the clamp was inversely related to the glucose-induced glucagon suppression and positively related to β-cell function. Growth hormone responses to hypoglycemia were lower in patients with type 2 diabetes (P = 0.0002) but not in patients with chronic pancreatitis.

α-Cell responses to oral glucose ingestion and to hypoglycemia are disturbed in patients with diabetes and chronic pancreatitis and in patients with type 2 diabetes. The similarities between these defects suggest a common etiology.

To investigate the association of falling insulin requirements (FIR) among women with preexisting diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy.

A multicenter prospective cohort study of 158 women (41 with type 1 diabetes and 117 with type 2 diabetes) was conducted. Women with FIR of ≥15% from the peak total daily dose after 20 weeks' gestation were considered case subjects (n = 32). The primary outcome was a composite of clinical markers of placental dysfunction (preeclampsia, small for gestational age [≤5th centile], stillbirth, premature delivery [<30 weeks], and placental abruption). Maternal circulating angiogenic markers (placental growth factor [PlGF] and soluble fms-like tyrosine kinase 1 [sFlt-1]), placental hormones (human placental lactogen, progesterone, and tumor necrosis factor-α), HbA_1c, and creatinine were studied serially during pregnancy.

FIR ≥15% were associated with an increased risk of the composite primary outcome (odds ratio [OR] 4.38 [95% CI 1.9–10.3]; P < 0.001), preeclampsia (OR 6.76 [95% CI 2.7–16.7]; P < 0.001), and was more common among women with type 1 diabetes (36.6 vs. 14.5%; P = 0.002). Creatinine was modestly elevated among women with FIR ≥15%; however, there was no difference in HbA_1c. The ratio of sFlt-1 to PlGF was significantly higher among women with FIR at 25, 30, and 36 weeks, with differences maintained in the subgroup that developed preeclampsia. There was no difference in placental hormones between the groups.

This is the first prospective study to associate FIR with altered expression of placental antiangiogenic factors and preeclampsia. FIR are an important clinical sign, among women with preexisting diabetes, that should alert the clinician to investigate underlying placental dysfunction.

To assess participant-level results from the first 4 years of implementation of the National Diabetes Prevention Program (National DPP), a national effort to prevent type 2 diabetes in those at risk through structured lifestyle change programs.

Descriptive analysis was performed on data from 14,747 adults enrolled in year-long type 2 diabetes prevention programs during the period February 2012 through January 2016. Data on attendance, weight, and physical activity minutes were summarized and predictors of weight loss were examined using a mixed linear model. All analyses were performed using SAS 9.3.

Participants attended a median of 14 sessions over an average of 172 days in the program (median 134 days). Overall, 35.5% achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%). Participants reported a weekly average of 152 min of physical activity (median 128 min), with 41.8% meeting the physical activity goal of 150 min per week. For every additional session attended and every 30 min of activity reported, participants lost 0.3% of body weight (P < 0.0001).

During the first 4 years, the National DPP has achieved widespread implementation of the lifestyle change program to prevent type 2 diabetes, with promising early results. Greater duration and intensity of session attendance resulted in a higher percent of body weight loss overall and for subgroups. Focusing on retention may reduce disparities and improve overall program results. Further program expansion and investigation is needed to continue lowering the burden of type 2 diabetes nationally.

Internet-based secure messaging between patients and providers through a patient portal is now common in the practice of modern medicine. There is limited evidence on how messaging is associated with use and clinical quality measures among patients with type 2 diabetes. We examine whether messaging with physicians for medical advice is associated with fewer face-to-face visits and better diabetes management.

Patients with diabetes who were enrolled in an online portal of an outpatient health care organization in 2011–2014 were studied (N = 37,762 patient-years). Messages from/to primary care physicians or diabetes-related specialists for medical advice were considered. We estimated the association of messaging with diabetes quality measures, adjusting for patient and provider characteristics and patient-level clustering.

Most patients (72%) used messaging, and those who made frequent visits were also more likely to message. Given visit frequency, no (vs. any) messaging was negatively associated with the likelihood of meeting an HbA_1c target of <8% (64 mmol/mol) (odds ratio [OR] 0.83 [95% CI 0.77, 0.90]). Among message users, additional messages (vs. 1) were associated with better outcome (two more messages: OR 1.17 [95% CI 1.06, 1.28]; three more messages: 1.38 [1.25, 1.53]; four more messages: 1.55 [1.43, 1.69]). The relationship was stronger for noninsulin users. Message frequency was also positively associated, but to a smaller extent, with process measures (e.g., eye examination). Physician-initiated messages had effects similar to those for patient-initiated messages.

Patients with diabetes frequently used secure messaging for medical advice in addition to routine visits to care providers. Messaging was positively associated with better diabetes management in a large community outpatient practice.

Type 2 diabetes is growing in epidemic proportions and disproportionately affects lower-income, diverse communities. Text messaging may provide one of the most rapid methods to overcome the "digital divide" to improve care.

A randomized, nonblinded, parallel-groups clinical trial design allocated N = 126 low-income, Hispanic participants with poorly controlled type 2 diabetes to receive the Dulce Digital intervention or usual care (UC). Dulce Digital participants received up to three motivational, educational, and/or call-to-action text messages per day over 6 months. The primary outcome was HbA_1c; lipids, blood pressure, and BMI were secondary outcomes. Satisfaction and acceptability were evaluated via focus groups and self-report survey items.

The majority of patients were middle-aged (mean age 48.43 years, SD 9.80), female (75%), born in Mexico (91%), and uninsured (75%) and reported less than a ninth-grade education level (73%) and mean baseline HbA_1c 9.5% (80 mmol/mol), SD 1.3, and fasting plasma glucose 187.17 mg/dL, SD 64.75. A statistically significant time-by-group interaction effect indicated that the Dulce Digital group achieved a significantly greater reduction in HbA_1c over time compared with UC (P = 0.03). No statistically significant effects were observed for secondary clinical indicators. The number of blood glucose values texted in by participants was a statistically significant predictor of month 6 HbA_1c (P < 0.05). Satisfaction and acceptability ratings for the Dulce Digital intervention were high.

Use of a simple, low-cost text messaging program was found to be highly acceptable in this sample of high-risk, Hispanic individuals with type 2 diabetes and resulted in greater improvement in glycemic control compared with UC.

To assess, in a randomized, double-blind, and placebo-controlled trial, the efficacy and safety of diacerein, an immune modulator anti-inflammatory drug, in improving glycemic control of patients with type 2 diabetes.

Eighty-four patients with HbA_1c between 7.5 and 9.5% (58–80 mmol/mol) were randomized to 48-week treatment with placebo (n = 41) or diacerein 100 mg/day (n = 43). The primary outcome was the difference in mean HbA_1c changes during treatment. Secondary outcomes were other efficacy and safety measurements. A general linear regression with repeated measures, adjusted for age, sex, diabetes duration, and each baseline value, was used to estimate differences in mean changes. Both intention-to-treat (ITT) analysis and per-protocol analysis (excluding 10 patients who interrupted treatment) were performed.

Diacerein reduced HbA_1c compared with placebo by 0.35% (3.8 mmol/mol; P = 0.038) in the ITT analysis and by 0.41% (4.5 mmol/mol; P = 0.023) in the per-protocol analysis. The peak of effect occurred at the 24th week of treatment (–0.61% [6.7 mmol/mol; P = 0.014] and –0.78% [8.5 mmol/mol; P = 0.005], respectively), but it attenuated toward nonsignificant differences at the 48th week. No significant effect of diacerein was observed in other efficacy and safety measures. Diarrhea occurred in 65% of patients receiving diacerein and caused treatment interruption in 16%. Seven patients in the diacerein group reduced insulin dosage, whereas 10 in the placebo group increased it; however, mild hypoglycemic events were equally observed.

Diacerein reduced mean HbA_1c levels, with peak of effect at the 24th week of treatment. The drug was well tolerated and may be indicated as adjunct treatment in patients with type 2 diabetes, particularly in those with osteoarthritis.

To compare the efficacy of ipragliflozin versus pioglitazone in patients with type 2 diabetes complicated by nonalcoholic fatty liver disease (NAFLD).

In this open-label, randomized, active-controlled trial, we randomly assigned 66 patients with type 2 diabetes and NAFLD to receive ipragliflozin 50 mg (n = 32) or pioglitazone 15–30 mg (n = 34) orally once daily. The primary outcome was a change from baseline in the liver-to-spleen attenuation ratio (L/S ratio) on computed tomography at week 24.

At week 24, the mean ± SD L/S ratio had increased by 0.22 (from 0.80 ± 0.24 to 1.00 ± 0.18) in the ipragliflozin group and 0.21 (from 0.78 ± 0.26 to 0.98 ± 0.16) in the pioglitazone group (P = 0.90). Serum aspartate and alanine aminotransferase levels, HbA_1c, and fasting plasma glucose were similarly reduced in the two treatment groups. Nevertheless, body weight and visceral fat area showed significant reductions only in the ipragliflozin group compared with the pioglitazone group (P < 0.0001 and P = 0.0013, respectively). There were no serious adverse events in either group.

Compared with pioglitazone, ipragliflozin exerts equally beneficial effects on NAFLD and glycemic control during the treatment of patients with type 2 diabetes complicated by NAFLD. Furthermore, ipragliflozin significantly reduced body weight and abdominal fat area.

This study investigated the association between renal histology, as assessed by morphometric analysis using light (LM) and electron (EM) microscopy, and changes in urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in Japanese people with type 2 diabetes in the early stages of diabetic nephropathy.

We performed percutaneous renal biopsies in 29 patients with type 2 diabetes (22 men, mean ± SD age 49 ± 10 years and GFR 119 ± 27 mL/min/1.73 m², with 15 normoalbuminuric [UAE <20 μg/min] and 14 microalbuminuric [UAE 20–200 μg/min]) to clarify which histological factors were associated with changes in UAE and GFR during 8.0 ± 3.5 years’ follow-up. Glomerular structural changes including mesangial volume fraction [Vv(Mes/glom)] were estimated using EM, whereas the index of arteriolar hyalinosis (IAH) score was assessed by LM. Patients underwent annual measurement of GFR using iohexol injection with simultaneous urine collections for UAE.

Vv(Mes/glom) was negatively correlated with baseline and follow-up GFR but not with UAE. The IAH score was positively correlated with UAE and negatively correlated with GFR at follow-up, but it was not correlated with either UAE or GFR at baseline. GFR at follow-up was significantly decreased from baseline in patients with IAH scores ≥2.0 and significantly lower than in patients with IAH scores <2.0. Patients with IAH scores <2.0 showed no significant change in GFR during follow-up.

Arteriolar hyalinosis is an additional histological predictor for albuminuria increase and GFR decline in normo- and microalbuminuric Japanese people with type 2 diabetes.

This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status.

RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes.

Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes.

All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.

The human vitamin E–binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR).

Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes.

Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95% CI 1.12–1.26], P = 5.96 x 10^–8). Afamin was positively associated with IR assessed by HOMA-IR (β 0.110 [95% CI 0.089–0.132], P = 1.37 x 10^–23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23–1.38], P = 3.53 x 10^–19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model.

This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.

Although patients with type 1 diabetes have a poor prognosis after a stroke, predictors of survival after an incident stroke in these patients are poorly studied.

In this observational study, a total of 144 patients of 4,083 with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study suffered an incident stroke in 1997–2010, and were followed for a mean 3.4 ± 3.1 years after the stroke. Information was recorded on hard cardiovascular events and death as a result of cardiovascular or diabetes-related cause, collectively referred to as vascular composite end point. Information was collected from medical records, death certificates, and the National Care Register of Health Care. Predictors at the time of the incident stroke were studied for the end points.

During follow-up, 104 (72%) patients suffered a vascular composite end point. Of these, 33 (32%) had a recurrent stroke, 33 (32%) a hard cardiovascular event, and 76 (53%) died of cardiovascular or diabetes-related causes, with an overall 1-year survival of 76% and 5-year survival of 58%. The predictors of a vascular composite end point were hemorrhagic stroke subtype (hazard ratio 2.03 [95% CI 1.29–3.19]), as well as chronic kidney disease stage 2 (2.48 [1.17–5.24]), stage 3 (3.04 [1.54–6.04]), stage 4 (3.95 [1.72–9.04]), and stage 5 (6.71 [3.14–14.34]). All-cause mortality increased with deteriorating kidney function.

Patients with type 1 diabetes with an incident stroke have a poor cardiovascular prognosis and a high risk of all-cause mortality. In particular, hemorrhagic stroke subtype and progression of diabetic kidney disease conveys worse outcome.

To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT).

This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia.

Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05).

In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.