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Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes

Manell, Hannes (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi
Staaf, Johan (author)
Uppsala universitet,Pediatrik,Institutionen för medicinsk cellbiologi
Manukyan, Levon (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi
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Kristinsson, Hjalti (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi
Cen, Jing (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi
Stenlid, Rasmus (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi
Ciba, Iris (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi,Pediatrik
Forslund, Anders (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi,Pediatrik
Bergsten, Peter (author)
Uppsala universitet,Institutionen för medicinsk cellbiologi
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 (creator_code:org_t)
The Endocrine Society, 2016
2016
English.
In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:3, s. 1181-1189
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • CONTEXT: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).OBJECTIVE: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.DESIGN: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).SETTING: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.PATIENTS AND PARTICIPANTS: Adolescents with obesity, age 10-18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included.MAIN OUTCOME MEASURES: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.RESULTS: Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001).CONCLUSIONS: Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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