Effect of Excessive Weight Gain With Intensive Therapy of Type 1 Diabetes on Lipid Levels and Blood Pressure

Purnell, Jonathan Q.; Hokanson, John E.; Marcovina, Santica M.; Steffes, Michael W.; Cleary, Patricia A.; Brunzell, John D.

doi:10.1001/jama.280.2.140

Cited by 418 publications

(375 citation statements)

References 21 publications

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“…The study also confirms that, as is the case in nondiabetic subjects, most E2/2 subjects have low lipids, and that only with a second hit, such as the weight gain with intensive diabetes therapy [32], which occurred in the one hyperlipidemic E2/2 subject, that the effect of the e2 allele is manifested as hyperlipidemia and remnant removal disease. The study also demonstrates that the frequency of apo E2 homozygosity in these Type 1 diabetic subjects is similar to that of the normal population (0.7% versus 0.8%, respectively).…”

Section: Resultssupporting

confidence: 77%

“…It confirms that only with a second hit, such as the weight gain with intensive diabetes therapy [32] that occurred in the one hyperlipidemic E2/2 subject, that the effect of the e2 allele is manifested as hyperlipidemia and severe remnant removal disease.…”

Section: Discussionsupporting

confidence: 53%

“…Given that one of the E2/2 subjects was hyperlipidemic (subject #4, Table 1), this subject's distribution is shown separately from the average of the five normolipidemic E2/2 subjects. Compared to the E3/3 subjects, the dyslipidemic E2/2 subject demonstrated an increase in VLDL (in fractions 28-37) particularly in the dense VLDL (VLDL remnants) (in fractions [31][32][33][34][35] and in IDL (in fractions [17][18][19][20][21][22][23][24][25][26][27][28][29][30]. In the absence of this dyslipidemic subject, the VLDL and IDL cholesterol distribution of the remaining normolipidemic E2/2 subjects were similar to, but appeared to be slightly higher, than that of the E3/3 subjects (Fig.…”

Section: Resultsmentioning

confidence: 95%

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LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

et al. 2007

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Apo E plays an important role in chylomicron and VLDL remnant processing, uptake or conversion to LDL. The type of lipoprotein that isolates in the LDL density of E2/2 subjects was investigated and the effect of the apo E isoforms on LDL mass was determined in all genotypes in a large group of Type 1 diabetics. Analysis of the LDL composition of E2/2 homozygotes (n = 6) compared to subjects with the common E3/3 isoform (n = 6) demonstrated an enrichment in apo E, unesterified cholesterol, phospholipid and triglyceride relative to apo B in E2/2 subjects, more typical of a dense IDL remnant than of LDL. Although diabetics were studied, these findings are considered to reflect those of the general population. Comparison of the lipoprotein distribution of homozygous and heterozygous subjects revealed that, as genotype changed from E4/4 (n = 22) to E3/4 (n = 262), E3/3 (n = 710) = E2/4 (n = 30), E2/3 (n = 151), E2/2 (n = 6), LDL cholesterol decreased significantly in a stepwise manner. The decrease was not in a specific subgroup of LDL. In conclusion, for E2/2 subjects, lipoproteins isolated in the LDL density range appear to be composed mainly of dense IDL remnants and some Lp(a). The apo E isoform also has a significant effect on LDL concentration in both homozygotes and heterozygotes.

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Section: Resultssupporting

confidence: 77%

Section: Discussionsupporting

confidence: 53%

Section: Resultsmentioning

confidence: 95%

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LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

et al. 2007

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“…This has been demonstrated in large-scale studies [9,10]. Excessive weight gain has been identified as a major concern with long-term intensive therapy of Type 1 diabetes mellitus [26]. In this trial, a significantly lower mean body weight was observed in the insulin detemir/insulin aspart group than in the NPH/regular human insulin group after 18 weeks of treatment.…”

Section: Discussionmentioning

confidence: 54%

Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with Type 1 diabetes

Fontaine²,

et al. 2004

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Aims/hypothesis. The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin. Methods. In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively. Results. Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA 1 c: 7.88% vs 8.11%; mean difference: −0.22% point [95% CI: −0.34 to −0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA 1 c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001). Conclusions/interpretation. Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.

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“…This, in turn, may impair treatment adherence and impede therapy intensification, with consequent failure to achieve glycaemic goals 1, 2. Weight gain is associated with an increased risk of coronary heart and cardiovascular disease in people with diabetes 3, 4, a troubling prospect given that 80–90% of people with T2D are already overweight before insulin replacement 5. Landmark trials, notably the UK Prospective Diabetes Study 6 and the Diabetes Control and Complications Trial 7, showed that the cost of improved glycaemic control was considerable weight gain with intensive treatment regimens.…”

Section: Introductionmentioning

confidence: 99%

Weight‐sparing effect of insulin detemir: a consequence of central nervous system‐mediated reduced energy intake?

Russell‐Jones

Danne

Hermansen

et al. 2015

Diabetes Obesity Metabolism

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Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight‐sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter‐regulatory response to insulin through restoration of the hepatic–peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.

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Effect of Excessive Weight Gain With Intensive Therapy of Type 1 Diabetes on Lipid Levels and Blood Pressure

Cited by 418 publications

References 21 publications

LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

LDL composition in E2/2 subjects and LDL distribution by Apo E genotype in type 1 diabetes

Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with Type 1 diabetes

Weight‐sparing effect of insulin detemir: a consequence of central nervous system‐mediated reduced energy intake?

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