Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects

Šindelka, G; Heinemann, Lutz; Berger, Michael; Frenck, W.; Chantelau, Ernst

doi:10.1007/bf00408474

Cited by 101 publications

(87 citation statements)

References 10 publications

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“…On the other hand, consistent with the present data, studies performed in type 1 diabetic patients have demonstrated significantly slower insulin absorption, measured as residual radioactivity at the injection site, in obese than in nonobese patients (11,12). As in the present study, however, subcutaneous fat thickness did not explain variation in insulin requirements in these studies (11,12). Because inhibition of endogenous glucose production represents the major target for insulin therapy (34,35), we were particularly interested in searching for parameters that might explain interindividual variation in hepatic insulin sensitivity.…”

Section: A B C Dsupporting

confidence: 92%

“…In that study, which included obese and nonobese patients, no correlation was observed between depth of the fat layer and residual radioactivity at the 3 injection sites examined (15). On the other hand, consistent with the present data, studies performed in type 1 diabetic patients have demonstrated significantly slower insulin absorption, measured as residual radioactivity at the injection site, in obese than in nonobese patients (11,12). As in the present study, however, subcutaneous fat thickness did not explain variation in insulin requirements in these studies (11,12).…”

Section: A B C Dsupporting

confidence: 88%

“…Previous insulin absorption studies have been performed almost exclusively in patients with type 1 diabetes using iodinated insulin ([ 125 I]-labeled regular insulin) to trace insulin absorption (4)(5)(6)(7)(8)(9). Those studies have shown that insulin absorption, at constant temperature under resting conditions, is slowed by increases in subcutaneous fat thickness (10,11), total dose injected (9), decrease in subcutaneous blood flow (6,12,13), and injection site (10). Insulin antibodies have not been found to influence insulin requirements (5), nor has the amount of insulin absorbed been shown to correlate with insulin action in normal subjects (14).…”

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confidence: 99%

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Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients.

et al. 2000

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To determine causes of interindividual variation in insulin requirements, we recruited 20 type 2 diabetic patients with stable glucose control and insulin doses for >1 year on combination therapy with bedtime NPH insulin and metformin. Insulin absorption (increase in free and total insulin over 8 h after a subcutaneous dose of regular insulin) and actions of intravenous (6-h 0.3 mU · kg -1 · min -1 euglycemic insulin clamp combined with [3-3 H]glucose) and subcutaneous (glucose infusion rate required to maintain isoglycemia and suppression of free fatty acids [FFAs]) insulin, liver fat content (proton spectroscopy), visceral fat (magnetic resonance imaging), weight, and body composition were determined. We found the following variation in parameters: insulin dose range 10-176 U (mean 42 U, fold variation 17.6؋) or 0.13-1.39 U/kg (0.44 U/kg, 10.7؋), absorbed insulin 10.6؋, action of subcutaneous insulin to suppress FFAs 7.5؋ and to stimulate glucose metabolism (M value) 11.5؋, body weight 67-127 kg (91 kg, 1.9؋), liver fat 2-28% (12%, 14؋), and visceral fat 179-2,053 ml (1,114 ml, 11.5؋). The amount of insulin absorbed, measured as either free or total insulin, was significantly correlated with its ability to suppress FFAs and stimulate glucose metabolism but not with the insulin dose per se. The actions of absorbed insulin were, on the other hand, significantly correlated with the daily insulin dose (r = 0.70 for action on FFAs, P < 0.001, and r = -0.61 for M value, P < 0.005). Actions of subcutaneous and intravenous insulin to suppress FFAs were significantly correlated (r = 0.82, P < 0.001, R 2 = 67%). Of the measures of adiposity, the percent hepatic fat was the parameter best correlated with the daily insulin dose (r = 0.76, P < 0.001). The percent hepatic fat was also significantly correlated with the ability of intravenous insulin to suppress endogenous glucose production (r = 0.72, P < 0.005). We conclude that the major reason for interindividual variation in insulin requirements in type 2 diabetes is the variation in insulin action. Variation in hepatic fat content may influence insulin requirements via an effect on the sensitivity of endogenous glucose production to insulin. Diabetes 49:749-758, 2000

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Section: A B C Dsupporting

confidence: 92%

Section: A B C Dsupporting

confidence: 88%

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confidence: 99%

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Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients.

et al. 2000

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“…Insulin absorption rate correlated positively between insulin and glucagon, while MCR correlated negatively. fat thickness decelerates insulin absorption 14 and is likely to affect glucagon pharmacokinetics. There is also evidence that higher body fat might influence insulin and glucagon action.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Insulin Aspart and Glucagon in Type 1 Diabetes during Closed-Loop Operation

Haidar

Duval

Legault

et al. 2013

J Diabetes Sci Technol

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“…It is well known that increased SC thickness alters insulin absorption, shifting the time-action profile curves to the right. 12 In a phase I, randomised, euglycaemic clamp study, a group of non-diabetic obese subjects received a single injection of insulin glulisine, insulin lispro or RHI (0.3U/kg SC). 13 As expected, time to onset of glucose infusion was shorter, and maximal glucose insulin rates were greater for insulin glulisine and insulin lispro compared with RHI (see Figure 2).…”

Section: Insulin Glulisine -A New Formulationmentioning

confidence: 99%

Potential Advantages of a Basal–Bolus Regimen Using Insulin Glulisine as Prandial Insulin

Ampudia‐Blasco¹

2007

European Endocrinology

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Several interventional studies have demonstrated that achieving near-normal glycaemic control by means of intensive insulin therapy is the best strategy to avoid and slow the progression of chronic complications in type 1 and type 2 diabetes. 1-3 Interestingly, the In the last 15 years, new insulin formulations have been coming into the market. First, short-acting insulin analogues (SAIAs) were developed to reproduce the physiological prandial insulin response, which is rapid, powerful and of short duration. 5 More recently, long-acting insulin analogues (LAIAs) were introduced to replace basal insulin secretion, which is peakless, sustained and necessary to avoid excessive hepatic glucose production. 5 Insulin glulisine is the most recently marketed SAIA -beside insulin lispro and insulin aspart -and is available to be used as prandial insulin in adults with type 1 and type 2 diabetes. In this article, the potential advantages of insulin glulisine will be discussed, as well as its role as prandial insulin in a basal-bolus regimen.

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Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects

Cited by 101 publications

References 10 publications

Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients.

Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients.

Pharmacokinetics of Insulin Aspart and Glucagon in Type 1 Diabetes during Closed-Loop Operation

Potential Advantages of a Basal–Bolus Regimen Using Insulin Glulisine as Prandial Insulin

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