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Ilkka Vauhkonen, Leo Niskanen, Mikael Knip, Leena Moilanen Mykkänen, Steven Haffner, Matti Uusitupa and Markku Laakso

Objective: We set out to assess whether hyperproinsulinaemia is an early finding in latent autoimmune diabetes in adults (LADA).

Research design and methods: We measured plasma proinsulin and C-peptide responses during a 2-h oral glucose tolerance test (OGTT) and in the hyperglycaemic clamp in 21 normoglycaemic offspring of LADA patients testing positive for glutamic acid decarboxylase antibodies (GADA) or islet cell antibodies (ICA), and in 17 healthy control subjects without a family history of diabetes.

Results: The study groups had comparable areas under the curves of blood glucose, plasma proinsulin, C-peptide and proinsulin/C-peptide in the OGTT. However, the offspring of LADA patients had higher proinsulin/C-peptide in the hyperglycaemic clamp (P < 0.01 versus the control group). The offspring of GADA-positive LADA patients (n = 9) had higher proinsulin and proinsulin/C-peptide than did the control group in the OGTT (P < 0.05 for both comparisons) and in the hyperglycaemic clamp (P < 0.001 and P < 0.05 respectively). They also had higher proinsulin than the offspring of ICA-positive LADA patients (n = 12) (P < 0.001) in the hyperglycaemic clamp. The offspring of ICA-positive LADA patients did not clearly show hyperproinsulinaemia during the tests, but they had lower maximal glucose-stimulated insulin secretory capacity than the control group (P < 0.05) and the offspring of GADA-positive LADA patients (P < 0.05) in the hyperglycaemic clamp.

Conclusions: These results suggested that insulin secretion in the offspring of GADA-positive LADA patients is characterised by subtle defects in the processing of insulin precursors. Furthermore, various proinsulin responses among the offspring of LADA patients with different autoimmune markers provided further evidence that LADA is a heterogeneous disorder.

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Hanna Huopio, Henna Cederberg, Jagadish Vangipurapu, Heidi Hakkarainen, Mirja Pääkkönen, Teemu Kuulasmaa, Seppo Heinonen and Markku Laakso


The aim of this study was to investigate the association of risk variants for type 2 diabetes (T2D) and hyperglycemia with gestational diabetes (GDM).

Design and methods

Five hundred and thirty-three Finnish women who were diagnosed with GDM and 407 controls with normal glucose tolerance during the pregnancy were genotyped for 69 single-nucleotide polymorphisms (SNPs) which have been previously verified as susceptibility risk variants for T2D and hyperglycemia. All participants underwent an oral glucose tolerance test at the follow-up study after the index pregnancy.


Risk variants rs10830963 and rs1387153 of MTNR1B were significantly associated with GDM (odds ratio (OR)=1.62 (95% CI 1.34–1.96), P=4.5×10−7 and 1.38 (1.14–1.66), P=7.6×10−4 respectively). Both SNPs of MTNR1B were also significantly associated with elevated fasting glucose level and reduced insulin secretion at follow-up. Additionally, risk variants rs9939609 of FTO, rs2796441 of TLE1, rs560887 of G6PC2, rs780094 of GCKR, rs7903146 of TCF7L2 and rs11708067 of ADCY5 showed nominally significant associations with GDM (OR range from 1.25 to 1.30).


Our study suggests that GDM and T2D share a similar genetic background. Our findings also provide further evidence that risk variants of MTNR1B are associated with GDM by increasing fasting plasma glucose and decreasing insulin secretion.

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Henna Cederberg, Ulla Rajala, Vesa-Matti Koivisto, Jari Jokelainen, Heljä-Marja Surcel, Sirkka Keinänen-Kiukaanniemi and Markku Laakso


Ghrelin, a gut–brain peptide involved in energy homeostasis, circulates predominantly (>90%) in unacylated form. Previous studies, however, have focused on total and acylated ghrelin, and the role of unacylated ghrelin (UAG) is not well understood. Particularly, the association of UAG with weight loss and changes in body composition in adults remains unclear. We hypothesized that exercise-associated increase in UAG level is associated with weight loss, favorable changes in body composition, and body fat distribution.

Design and methods

A prospective study of 552 young men (mean age 19.3 and range 19–28 years) undergoing military service with structured 6-month exercise training program. Exercise performance, body composition, and biochemical measurements were obtained at baseline and follow-up. Association between changes in UAG levels and body composition and body fat distribution were evaluated.


An increase in UAG level during the exercise intervention was associated with reduced weight, fat mass (FM), fat percentage (fat %), and waist circumference, but not with fat-free mass. Inverse associations of changes in UAG level with changes in waist circumference and fat % were independent of weight at baseline, and changes in weight and exercise performance. Associations of changes in UAG level with waist circumference were significantly stronger than with fat % after the adjustment for confounding variables.


UAG is associated with changes in body weight and body composition during an intensive long-term exercise intervention in young men. The association of UAG levels with changes in central obesity was stronger than with total FM.