Intensive glucose-lowering: long-lasting benefits on albuminuria in patients with type 1 diabetes

2014 ◽  
Vol 10 (9) ◽  
pp. 481-481
Author(s):  
Susan J. Allison
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Lowering ◽  
Intensive Glucose Lowering

scholarly journals Pharmacokinetics and Pharmacodynamics of Three Different Formulations of Insulin Aspart: A Randomized, Double-blind, Crossover Study in Men With Type 1 Diabetes

2020 ◽  
Author(s):  
Eva Svehlikova ◽  
Ines Mursic ◽  
Thomas Augustin ◽  
Christoph Magnes ◽  
David Gerring ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Crossover Study ◽  
Insulin Aspart ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Onset Of Action ◽  
Double Blind ◽  
Glucose Lowering ◽  
Lowering Effect ◽  
Glucose Lowering Effect

OBJECTIVE <p>To investigate the pharmacokinetic and pharmacodynamic properties, and safety of a novel formulation of insulin aspart (AT247) versus currently marketed insulin aspart formulations (IAsp and faster IAsp).</p> <p> </p> <p>RESEARCH DESIGN AND METHODS</p> <p>This single-center, randomized, double-blind, three-period, crossover study was conducted in 19 men with type 1 diabetes, receiving single dosing of trial products (0.3 U/kg) in a random order on three visits. Pharmacokinetics and pharmacodynamics were assessed during a euglycemic clamp lasting up to 8 hours. </p> <p> </p> <p>RESULTS</p> <p>Onset of insulin appearance was earlier for AT247 compared with IAsp (−12 minutes [95% CI −14;−8] p=0.0004) and faster IAsp (−2 minutes [−5;−2] p=0.0003). Onset of action was accelerated compared with IAsp (−23 minutes [−37;−15] p=0.0004) and faster IAsp (−9 minutes [−11;−3] p=0.0006). Within the first 60 minutes, a higher exposure was observed for AT247 compared with IAsp (AUC<sub>Asp,0-60min</sub>: treatment ratio vs IAsp 2.3 [1.9;2.9]; vs faster IAsp 1.5 [1.3;1.8]), which was underpinned by a greater early glucose-lowering effect (AUC<sub>GIR,0-60min</sub>: treatment ratio vs IAsp 2.8 [2.0;5.5]; vs faster IAsp 1.7 [1.3;2.3]). Furthermore, an earlier offset of exposure was observed for AT247 compared with IAsp (−32 minutes [−58;−15] p=0.0015) and faster IAsp (−27 minutes [−85;−15] p=0.0017), while duration of glucose-lowering effect, measured by t<sub>Late50%GIRmax</sub>, did not differ significantly.</p> <p> </p> <p>CONCLUSIONS</p> <p>AT247 exhibited an earlier insulin appearance, exposure and offset, with corresponding enhanced early glucose-lowering effect compared with IAsp and faster IAsp. It therefore represents a promising candidate in the pursuit for second generation prandial insulin analogs to improve postprandial glycemic control.</p>

scholarly journals UCP1-independent glucose-lowering effect of leptin in type 1 diabetes: only in conditions of hypoleptinemia

2020 ◽  
Vol 318 (1) ◽  
pp. E72-E86
Author(s):  
Petr Zouhar ◽  
Günaj Rakipovski ◽  
Muhammad Hamza Bokhari ◽  
Oliver Busby ◽  
Johan F. Paulsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Therapeutic Potential ◽  
Uncoupling Protein ◽  
Leptin Resistance ◽  
Diabetic Mice ◽  
High Fat ◽  
Glucose Lowering ◽  
Lowering Effect ◽  
Glucose Lowering Effect

The possibility to use leptin therapeutically for lowering glucose levels in patients with type 1 diabetes has attracted interest. However, earlier animal models of type 1 diabetes are severely catabolic with very low endogenous leptin levels, unlike most patients with diabetes. Here, we aim to test glucose-lowering effects of leptin in novel, more human-like murine models. We examined the glucose-lowering potential of leptin in diabetic models of two types: streptozotocin-treated mice and mice treated with the insulin receptor antagonist S961. To prevent hypoleptinemia, we used combinations of thermoneutral temperature and high-fat feeding. Leptin fully normalized hyperglycemia in standard chow-fed streptozotocin-treated diabetic mice. However, more humanized physiological conditions (high-fat diets or thermoneutral temperatures) that increased adiposity — and thus also leptin levels — in the diabetic mice abrogated the effects of leptin, i.e., the mice developed leptin resistance also in this respect. The glucose-lowering effect of leptin was not dependent on the presence of the uncoupling protein-1 and was not associated with alterations in plasma insulin, insulin-like growth factor 1, food intake or corticosterone but fully correlated with decreased plasma glucagon levels and gluconeogenesis. An important implication of these observations is that the therapeutic potential of leptin as an additional treatment in patients with type 1 diabetes is probably limited. This is because such patients are treated with insulin and do not display low leptin levels. Thus, the potential for a glucose-lowering effect of leptin would already have been attained with standard insulin therapy, and further effects on blood glucose level through additional leptin cannot be anticipated.

scholarly journals Pharmacokinetics and Pharmacodynamics of Three Different Formulations of Insulin Aspart: A Randomized, Double-blind, Crossover Study in Men With Type 1 Diabetes

2020 ◽  
Author(s):  
Eva Svehlikova ◽  
Ines Mursic ◽  
Thomas Augustin ◽  
Christoph Magnes ◽  
David Gerring ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Crossover Study ◽  
Insulin Aspart ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Onset Of Action ◽  
Double Blind ◽  
Glucose Lowering ◽  
Lowering Effect ◽  
Glucose Lowering Effect

OBJECTIVE <p>To investigate the pharmacokinetic and pharmacodynamic properties, and safety of a novel formulation of insulin aspart (AT247) versus currently marketed insulin aspart formulations (IAsp and faster IAsp).</p> <p> </p> <p>RESEARCH DESIGN AND METHODS</p> <p>This single-center, randomized, double-blind, three-period, crossover study was conducted in 19 men with type 1 diabetes, receiving single dosing of trial products (0.3 U/kg) in a random order on three visits. Pharmacokinetics and pharmacodynamics were assessed during a euglycemic clamp lasting up to 8 hours. </p> <p> </p> <p>RESULTS</p> <p>Onset of insulin appearance was earlier for AT247 compared with IAsp (−12 minutes [95% CI −14;−8] p=0.0004) and faster IAsp (−2 minutes [−5;−2] p=0.0003). Onset of action was accelerated compared with IAsp (−23 minutes [−37;−15] p=0.0004) and faster IAsp (−9 minutes [−11;−3] p=0.0006). Within the first 60 minutes, a higher exposure was observed for AT247 compared with IAsp (AUC<sub>Asp,0-60min</sub>: treatment ratio vs IAsp 2.3 [1.9;2.9]; vs faster IAsp 1.5 [1.3;1.8]), which was underpinned by a greater early glucose-lowering effect (AUC<sub>GIR,0-60min</sub>: treatment ratio vs IAsp 2.8 [2.0;5.5]; vs faster IAsp 1.7 [1.3;2.3]). Furthermore, an earlier offset of exposure was observed for AT247 compared with IAsp (−32 minutes [−58;−15] p=0.0015) and faster IAsp (−27 minutes [−85;−15] p=0.0017), while duration of glucose-lowering effect, measured by t<sub>Late50%GIRmax</sub>, did not differ significantly.</p> <p> </p> <p>CONCLUSIONS</p> <p>AT247 exhibited an earlier insulin appearance, exposure and offset, with corresponding enhanced early glucose-lowering effect compared with IAsp and faster IAsp. It therefore represents a promising candidate in the pursuit for second generation prandial insulin analogs to improve postprandial glycemic control.</p>

scholarly journals Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study

2021 ◽  
Author(s):  
Rikke Viggers ◽  
Morten Hasselstrøm Jensen ◽  
Henrik Vitus Bering Laursen ◽  
Asbjørn Mohr Drewes ◽  
Peter Vestergaard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Diabetes Incidence ◽  
Secondary Diabetes ◽  
Glucose Lowering ◽  
Lowering Therapy ◽  
Glucose Lowering Therapy

<p><i>Objective</i>: Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared to type 1 and type 2 diabetes.</p> <p><i>Research Design and Methods:</i> In a Danish nation-wide population-based cohort study we identified all individuals with adult-onset diabetes mellitus in the period 2000-2018 and categorized them as type 1 diabetes, type 2 diabetes or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. </p> <p><i>Results</i><i>:</i> Among 398,456 adults with new-onset diabetes mellitus, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years vs. 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence-rate-ratio 0.6; 95% CI 0.6-0.7, p<0.001). A sizeable proportion of PPDM patients were classified as type 2 diabetes (44.9%) and were prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared to type 2 diabetes (hazard ratio 3.10; 95% CI 2.96-3.23, p<0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30; 95% CI 4.01-4.56, p<0.001).</p> <p><i>Conclusions</i><i>:</i> PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.</p>

scholarly journals Glucose-Lowering Therapy in Patients With Postpancreatitis Diabetes Mellitus: A Nationwide Population-Based Cohort Study

2021 ◽  
Author(s):  
Rikke Viggers ◽  
Morten Hasselstrøm Jensen ◽  
Henrik Vitus Bering Laursen ◽  
Asbjørn Mohr Drewes ◽  
Peter Vestergaard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Diabetes Incidence ◽  
Secondary Diabetes ◽  
Glucose Lowering ◽  
Lowering Therapy ◽  
Glucose Lowering Therapy

<p><i>Objective</i>: Postpancreatitis diabetes mellitus (PPDM) is a type of secondary diabetes that requires special considerations for management. The main objective was to examine prescription patterns of glucose-lowering therapy among adults with PPDM compared to type 1 and type 2 diabetes.</p> <p><i>Research Design and Methods:</i> In a Danish nation-wide population-based cohort study we identified all individuals with adult-onset diabetes mellitus in the period 2000-2018 and categorized them as type 1 diabetes, type 2 diabetes or PPDM. We ascertained diabetes incidence rates, clinical and demographic characteristics, classifications and prescription patterns of glucose-lowering therapy and compared these parameters across diabetes subgroups. </p> <p><i>Results</i><i>:</i> Among 398,456 adults with new-onset diabetes mellitus, 5,879 (1.5%) had PPDM, 9,252 (2.3%) type 1 diabetes and the remaining type 2 diabetes (96.2%). The incidence rate of PPDM was 7.9 (95% CI 7.7-8.1) per 100,000 person-years vs. 12.5 (95% CI 12.2-12.7) for type 1 diabetes (incidence-rate-ratio 0.6; 95% CI 0.6-0.7, p<0.001). A sizeable proportion of PPDM patients were classified as type 2 diabetes (44.9%) and were prescribed sulfonylureas (25.2%) and incretin-based therapies (18.0%) that can potentially be harmful in PPDM. In contrast, 35.0% of patients never received biguanides, which are associated with a survival benefit in PPDM. Increased insulin requirements were observed for patients with PPDM compared to type 2 diabetes (hazard ratio 3.10; 95% CI 2.96-3.23, p<0.001) in particular for PPDM associated with chronic pancreatitis (hazard ratio 4.30; 95% CI 4.01-4.56, p<0.001).</p> <p><i>Conclusions</i><i>:</i> PPDM is a common type of secondary diabetes in adults but is often misclassified and treated as type 2 diabetes, although PPDM requires special considerations for management.</p>

AICAR and phlorizin reverse the hypoglycemia-specific defect in glucagon secretion in the diabetic BB rat

2002 ◽  
Vol 283 (5) ◽  
pp. E1076-E1083 ◽  
Author(s):  
R. J. McCrimmon ◽  
M. L. Evans ◽  
R. J. Jacob ◽  
X. Fan ◽  
Y. Zhu ◽  
...  
Keyword(s):  
Animal Model ◽  
Type 1 Diabetes ◽  
Glucagon Secretion ◽  
Fold Increase ◽  
Bb Rat ◽  
Exogenous Insulin ◽  
Counterregulatory Hormones ◽  
Glucose Lowering ◽  
Bb Rats

Individuals with type 1 diabetes demonstrate a hypoglycemia-specific defect in glucagon secretion. To determine whether intraislet hyperinsulinemia plays a role in the genesis of this defect, glucagon-secretory responses to moderate hypoglycemia induced by either insulin or a novel combination of the noninsulin glucose-lowering agents 5-aminoimidazole-4-carboxamide (AICAR) and phlorizin were compared in diabetic BB rats (an animal model of type 1 diabetes) and nondiabetic BB rats. The phlorizin-AICAR combination was able to induce moderate and equivalent hypoglycemia in both diabetic and nondiabetic BB rats in the absence of marked hyperinsulinemia. Diabetic BB rats demonstrated impaired glucagon and epinephrine responses during insulin-induced hypoglycemia compared with nondiabetic rats. In contrast, both glucagon (9- to 10-fold increase) and epinephrine (5- to 6-fold increase) responses were markedly improved during phlorizin-AICAR hypoglycemia. Combining phlorizin, AICAR, and insulin attenuated the glucagon response to hypoglycemia by 70% in the diabetic BB rat. Phlorizin plus AICAR had no effect on counterregulatory hormones under euglycemic conditions. We conclude that α-cell glucagon secretion in response to hypoglycemia is not defective if intraislet hyperinsulinemia is prevented. This suggests that exogenous insulin plays a pivotal role in the etiology of this defect.

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