IMPORTANCEPrevious clinical trials showing the benefit of continuous glucose monitoring (CGM) in the management of type 1 diabetes predominantly have included adults using insulin pumps, even though the majority of adults with type 1 diabetes administer insulin by injection.OBJECTIVE To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections.DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practices in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A 1c (HbA 1c ) levels of 7.5% to 9.9%.INTERVENTIONS Random assignment 2:1 to CGM (n = 105) or usual care (control group; n = 53).MAIN OUTCOMES AND MEASURES Primary outcome measure was the difference in change in central-laboratory-measured HbA 1c level from baseline to 24 weeks. There were 18 secondary or exploratory end points, of which 15 are reported in this article, including duration of hypoglycemia at less than 70 mg/dL, measured with CGM for 7 days at 12 and 24 weeks. RESULTS Among the 158 randomized participants (mean age, 48 years [SD, 13]; 44% women; mean baseline HbA 1c level, 8.6% [SD, 0.6%]; and median diabetes duration, 19 years [interquartile range, 10-31 years]), 155 (98%) completed the study. In the CGM group, 93% used CGM 6 d/wk or more in month 6. Mean HbA 1c reduction from baseline was 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group and 0.5% and 0.4%, respectively, in the control group (repeated-measures model P < .001). At 24 weeks, the adjusted treatment-group difference in mean change in HbA 1c level from baseline was -0.6% (95% CI, -0.8% to -0.3%; P < .001). Median duration of hypoglycemia at less than <70 mg/dL was 43 min/d (IQR, 27-69) in the CGM group vs 80 min/d (IQR, in the control group (P = .002). Severe hypoglycemia events occurred in 2 participants in each group.CONCLUSIONS AND RELEVANCE Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA 1c level during 24 weeks. Further research is needed to assess longer-term effectiveness, as well as clinical outcomes and adverse effects.

Dexcom.

With the increasing success of islet transplantation, beta-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.

The contribution of gluconeogenesis (GNG) to endogenous glucose output (EGO) in type 2 diabetes is controversial. Little information is available on the separate influence of obesity on GNG. We measured percent GNG (by the 2 H 2 O technique) and EGO (by 6,6-[ 2 H]glucose) in 37 type 2 diabetic subjects (9 lean and 28 obese, mean fasting plasma glucose [FPG] 8.3 ± 0.3 mmol/l) and 18 control subjects (6 lean and 12 obese) after a 15-h fast. Percent GNG averaged 47 ± 5% in lean control subjects and was significantly increased in association with both obesity (P < 0.01) and diabetes (P = 0.004). By multivariate analysis, percent GNG was independently associated with BMI (partial r = 0.27, P < 0.05, with a predicted increase of 0.9% per BMI unit) and FPG (partial r = 0.44, P = 0.0009, with a predicted increase of 2.7% per mmol/l of FPG). In contrast, EGO was increased in both lean and obese diabetic subjects (15.6 ± 0.5 µmol · min -1 · kg -1 of fat-free mass, n = 37, P = 0.002) but not in obese nondiabetic control subjects (13.1 ± 0.7, NS) as compared with lean control subjects (12.4 ± 1.4). Consequently, gluconeogenic flux (percent GNG ؋ EGO) was increased in obesity (P = 0.01) and markedly elevated in diabetic subjects (P = 0.0004), whereas glycogenolytic flux was reduced only in association with obesity (P = 0.05). Fasting plasma glucagon levels were significantly increased in diabetic subjects (P < 0.05) and positively related to EGO, whereas plasma insulin was higher in obese control subjects than lean control subjects (P = 0.05) and unrelated to measured glucose fluxes. We conclude that the percent contribution of GNG to glucose release after a 15-h fast is independently and quantitatively related to the degree of overweight and the severity of fasting hyperglycemia. In obese individuals, reduced glycogenolysis ensures a normal rate of glucose output. In diabetic individuals, hyperglucagonemia contributes to inappropriately elevated rates of glucose output from both GNG and glycogenolysis. Diabetes 49:1367-1373, 2000 P atients with type 2 diabetes typically show an increase in endogenous glucose output (EGO) (1-3). Several observations indicate that gluconeogenesis (GNG) is increased in type 2 diabetes. First, there is an increased protein turnover and hence release of gluconeogenic amino acids. Second, in obese patients with type 2 diabetes, the increased fat mass and rate of lipolysis contribute substrate (glycerol) (4,5) and activation (free fatty acids) (6,7) for GNG. Third, the net uptake of all gluconeogenic precursor substrates by the liver is increased. Using splanchnic catheterization, Felig et al. (8) estimated that in diabetic subjects, conversion into glucose of gluconeogenic precursors could represent 30% of splanchnic glucose output versus 20% in lean nondiabetic subjects (8). Although net splanchnic substrate uptake cannot account for the whole of GNG, this finding is nevertheless compatible with enhanced GNG in diabetes. Finally, tracer studies have shown that in obese type 2 diabetic patients...