Eli Lilly and Company Insulins - A Century of Innovation.

Eli Lilly and Company has played a pivotal role in the development of insulin products since its discovery in 1921. Through their dedication to pharmaceutical innovation, Josiah K. Lilly Sr. and George HA Clowes, in close collaborations with the University of Toronto, made insulin commercially available in 1923. Other innovations include the development and commercialization of the first biosynthetic human insulin, a rapid-acting insulin analog and analog mixtures. Lilly has advanced the field of knowledge with significant efforts toward developing a hepatic preferential basal insulin. Other important insulin projects include the first concentrated rapid-acting insulin analog, clinical studies supporting the use of highly concentrated human insulin, and an advanced clinical development program for an ultra-rapid insulin analog. Lilly's commitment to people affected with diabetes remains strong and will continue into the future through collaborative research, innovative product development and investing in advanced technologies.

Impact of continuous glucose monitoring on diabetes management and marital relationships of adults with Type 1 diabetes and their spouses: a qualitative study.

AIMS: To examine the impact of continuous glucose monitoring on diabetes management and marital relationships of adults with Type 1 diabetes and their spouses. METHODS: Nine younger (30-49 years) and 11 older (50-70 years) patients with Type 1 diabetes and 14 spouses participated in eight focus groups specific to age and role (patient or spouse). Audio-recorded data were transcribed, coded and analysed using thematic analysis and aided by NVivo software. RESULTS: Qualitative analysis revealed participants perceived continuous glucose monitoring as positively influencing hypoglycaemia management by decreasing spouses' anxiety, vigilance and negative experiences. Participants also described continuous glucose monitoring as promoting collaborative diabetes management and increasing spousal understanding of diabetes, especially when planning and managing pregnancy. Couples' conflicts occurred when (1) patients assumed sole responsibility for continuous glucose monitoring and/or did not respond to night-time glucose alarms and (2) spouses did not understand alarms and felt frustrated and helpless to assist patients. CONCLUSIONS: Our findings suggest that continuous glucose monitoring may positively impact collaborative diabetes management and marital relationships of patients with Type 1 diabetes and their spouses. However, reluctance to collaborate and lack of understanding may contribute to couples' conflicts around continuous glucose monitoring. Our findings have important implications for clinical care and point to the need for interventions that include spouses in continuous glucose monitoring training to increase their understanding of continuous glucose monitoring, minimize risk for spousal conflict and enhance collaborative diabetes management. Further studies are needed to explore these issues in more detail and depth with larger and more diverse populations.

Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy.

PURPOSE: The authors investigated retinal blood flow changes in patients with insulin-dependent diabetes mellitus (IDDM) and no diabetic retinopathy compared to age-matched subjects without diabetes. They also investigated whether blood glucose levels could modulate retinal blood flow in these patients with diabetes and whether this modulation would impact retinal blood flow data used in cross-sectional studies assessing changes in retinal blood flow. METHODS: Retinal blood flow was measured using video fluorescein angiography, and blood glucose levels were manipulated using glucose clamp methodologies with continuous basal insulin replacement. Blood glucose levels were clamped at 100, 200, and 300 mg/dl. Retinal blood flow measurements were performed at each blood glucose level after subjects had been stabilized for an hour at each of the different blood glucose levels. RESULTS: Retinal blood flow was found to be significantly decreased (P< 0.01) in the group of patients with no diabetic retinopathy (19.4 +/- 4.6 arbitrary units [AU]) compared to retinal blood flow in subjects without diabetes (28.7 +/- 6.4 AU). During glucose clamp adjustment of blood glucose levels, it was found that as blood glucose levels were increased from euglycemia (100 mg/dl) to 200 mg/dl and to 300 mg/dl, retinal blood flow was significantly increased at the 200 mg/dl level (21.5 +/- 4.7 AU, P < 0.05) and at the 300 mg/dl level (25.9 +/- 8.8 AU, P <0.01) compared to the 100 mg/dl level (16.3 +/- 3.8 AU). In addition, the retinal blood flow at the 100 and 200 mg/dl levels was significantly reduced (P < 0.01) compared to nondiabetic retinal blood flow (28.7 +/- 6.4 AU). CONCLUSIONS: Retinal blood flow was found to be decreased in patients with IDDM with no diabetic retinopathy, and acute elevations in blood glucose levels resulted in increased retinal blood flow in these patients. The acute modulation of retinal blood flow by blood glucose levels should be considered in cross-sectional studies investigating retinal blood flow changes in patients with diabetes. The results from this study indicate that if blood glucose levels are not accounted for in the analyses, larger populations would have to be studied to demonstrate statistically significant differences between groups with and without diabetes.

Insulin modulates circulating endothelin-1 levels in humans.

Recent data indicate that insulin stimulates synthesis of the vasoconstrictor peptide endothelin-1 (ET-1) by cultured vascular endothelial cells in vitro. To determine whether insulin modulates ET levels in vivo and whether this effect is important in the pathogenesis of obesity-associated hypertension, we measured circulating immunoreactive ET-1 levels during euglycemic hyperinsulinemic clamps (20 mU/m2.min-1 for 120 minutes) in eight obese women (body mass index, 36 +/- 1 kg/m2) before and after 10 weeks on an 800-kcal/d protein-sparing liquid diet. During the clamp that preceded weight loss, insulin levels were increased from 17 +/- 2 to 51 +/- 3 mU/L and this was associated with an increment in ET-1 level from 28 +/- 3 to 33 +/- 3 pg/mL (P < .05). After weight loss, insulin levels were increased from 10 +/- 2 to 47 +/- 3 mU/L during the clamp, and there was a corresponding increase in ET-1 levels from 24 +/- 3 to 30 +/- 3 pg/mL (P < .025). The reduction in basal ET-1 level (from 28 +/- 3 to 24 +/- 3 pg/mL) with weight loss correlated strongly with the reduction in fasting immunoreactive insulin level (from 17 +/- 2 to 10 +/- 2 mU/L; r = .92, P < .01). The decrease in blood pressure with weight loss (from 130 +/- 6/73 +/- 3 to 118 +/- 4/72 +/- 3 mm Hg) did not correlate with the corresponding reduction in circulating ET-1 levels. These results indicate that insulin modulates ET-1 levels in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Disparate effects of weight loss on insulin sensitivity and erythrocyte sodium-lithium countertransport activity.

Previous investigations have demonstrated an association between impaired insulin sensitivity and elevated erythrocyte sodium-lithium countertransport (Na(+)-Li+ CT) activity. It has been speculated that insulin resistance and endogenous hyperinsulinemia are causally related to the development of elevated Na(+)-Li+ CT activity. To test this hypothesis, we measured insulin sensitivity (euglycemic insulin clamp technique) and Na(+)-Li+ CT activity in eight obese women before (weight = 102 +/- 5 kg) and after (weight = 88 +/- 5 kg; P < .001) a 10 week weight reduction program. Maximal velocity of Na(+)-Li+ CT activity did not change (0.50 +/- 0.09 v 0.49 +/- 0.10 mmol/L red blood cells/h; P = NS) despite the significant improvement in insulin sensitivity (73 +/- 12 vs 110 +/- 7 mg/m2/min; P < .0025) and reduction in fasting insulin levels (17 +/- 2 v 10 +/- 2 microU/mL; P < .05) that accompanied weight loss. These results suggest that insulin resistance and hyperinsulinemia are not linked pathophysiologically to the development of elevated Na(+)-Li+ CT activity.