Type 2 Diabetes: Hypoinsulinism, Hyperinsulinism, or Both?

The author discusses a new study reporting the birth weight of patients carrying a mutation in either of two closely related genes associated with maturity-onset diabetes of the young, testing the hypothesis that the primary defect caused by these genes results in decreased insulin secretion

Johdanto kompleksisiin moniarvoisiin funktioihin

Moniarvoisella funktiolla tarkoitetaan funktiota, jonka jotakin määrittelyjoukon alkiota vastaa useampi kuin yksi maalijoukon alkio. Voidaan ajatella, että funktio saa tällöin arvokseen maalijoukon alkion sijasta joukon maalijoukon alkioita. Kompleksianalyysissä etenkin monet alkeisfunktioiden käänteisfunktiot ovat moniarvoisia. Tässä työssä perehdytään kompleksianalyysin perustason oppikirjojen tapaan käsitellä moniarvoisia funktioita. Työssä määritellään moniarvoisiin funktioihin liittyvät käsitteet kiertopiste, haara ja leikkauskäyrä sekä havainnollistetaan näitä käsitteitä kompleksisen logaritmifunktion, yleisen potenssifunktion ja arkussinifunktion kautta. Lisäksi työssä perehdytään näiden kolmen esimerkkifunktion avulla siihen, miten moniarvoisia funktioita voidaan käsitellä yksiarvoisina ja analyyttisinä funktioina. Käsittelyn perusperiaate on se, että määrittelyjoukon jokaisella luvulla funktion arvoista valitaan sopivalla tavalla yksi, ja näin saatu yksiarvoinen funktion haara on analyyttinen jossain kompleksitason alueessa

PICMI: mapping point mutations on genomes

Motivation: Several international collaborations and local projects are producing extensive catalogues of genomic variations that are supplementing existing collections such as the OMIM catalogue. The flood of this type of data will keep increasing and, especially, it will be relevant to a wider user base, including not only molecular biologists, geneticists and bioinformaticians, but also clinical researchers. Mapping the observed variations, sometimes only described at the amino acid level, on a genome, identifying whether they affect a gene and—if so—whether they also affect different isoforms of the same gene, is a time consuming and often frustrating task

Delivery of an LGA infant and the maternal risk of diabetes: A prospective cohort study

Aims: Was to determine whether the birth weight of the infant predicts prediabetes (impaired fasting glucose, impaired glucose tolerance, or both) and type 2 diabetes (T2DM) during long-term follow-up of women with or without gestational diabetes mellitus (GDM). Methods: The women with or without GDM during their pregnancies in Kuopio University Hospital in 1989-2009 (n=876) were contacted and invited for an evaluation. They were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n = 662) and >90th percentile (large-for-gestational-age; LGA) (n = 116). Glucose tolerance was investigated with an oral glucose tolerance test after a mean follow-up time of 7.3 (SD 5.1) years. Results: The incidence of T2DM was 11.8% and 0% in the women with and without GDM, respectively, after an LGA delivery. The incidence of prediabetes increased with offspring birth weight categories in the women with and without GDM: from 46.3% and 26.2% (AGA) to 52.9% and 29.2% (LGA), respectively. Conclusions: GDM women with LGA infants are at an increased risk for subsequent development of T2DM and therefore represent a target group for intervention to delay or prevent T2DM development. In contrast, an LGA delivery without GDM does not increase T2DM risk. (C) 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Long-Term Outcome and Treatment in Persistent and Transient Congenital Hyperinsulinism : A Finnish Population-Based Study

Context: The management of congenital hyperinsulinism (CHI) has improved. Objective: To examine the treatment and long-term outcome of Finnish patients with persistent and transient CHI (P-CHI and T-CHI). Design: A population-based retrospective study of CHI patients treated from 1972 to 2015. Patients: 106 patients with P-CHI and 132 patients with T-CHI (in total, 42 diagnosed before and 196 after year 2000) with median follow-up durations of 12.5 and 6.2 years, respectively. Main outcome measures: Recovery, diabetes, pancreatic exocrine dysfunction, neurodevelopment. Results: The overall incidence of CHI (n = 238) was 1:11 300 live births (1972-2015). From 2000 to 2015, the incidence of P-CHI (n = 69) was 1:13 500 and of T-CHI (n = 127) 1:7400 live births. In the 21st century P-CHI group, hyperinsulinemic medication was initiated and normoglycemia achieved faster relative to earlier. Of the 74 medically treated P-CHI patients, 68% had discontinued medication. Thirteen (12%) P-CHI patients had partial pancreatic resection and 19 (18%) underwent near-total pancreatectomy. Of these, 0% and 84% developed diabetes and 23% and 58% had clinical pancreatic exocrine dysfunction, respectively. Mild neurological difficulties (21% vs 16%, respectively) and intellectual disability (9% vs 5%, respectively) were as common in the P-CHI and T-CHI groups. However, the 21st century P-CHI patients had significantly more frequent normal neurodevelopment and significantly more infrequent diabetes and pancreatic exocrine dysfunction compared with those diagnosed earlier. Conclusions: Our results demonstrated improved treatment and long-term outcome in the 21st century P-CHI patients relative to earlier.Peer reviewe

Future risk of metabolic syndrome in women with a previous LGA delivery stratified by gestational glucose tolerance : a prospective cohort study

Background: Whether the delivery of a large-for-gestational-age (LGA) infant predicts future maternal metabolic syndrome (MetS) is not known. To this aim, we investigated the incidence of MetS and its components in women with or without a history of gestational diabetes mellitus (GDM) with a view to the birth weight of the offspring. Methods: Eight hundred seventy six women treated for their pregnancies in Kuopio University Hospital in 19892009 underwent a follow-up study (mean follow-up time 7.3 (SD 5.1) years), of whom 489 women with GDM and 385 normoglycemic controls. The women were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n = 662) and > 90th percentile (LGA) (n = 116). MetS and its components were evaluated in the follow-up study according to the International Diabetes Federation criteria. Results: LGA vs. AGA delivery was associated with a higher incidence of MetS at follow-up in women with a background of GDM (54.4% vs. 43.6%), but not in women without GDM. Conclusion: An LGA delivery in women with GDM is associated with a higher risk of future MetS and this group is optimal to study preventive measures for MetS. In contrast, an LGA delivery after a normoglycemic pregnancy was not associated with an increased future maternal MetS risk.Peer reviewe

Bone structure assessed with pQCT in prepubertal males with delayed puberty or congenital hypogonadotropic hypogonadism

Objective Congenital hypogonadotropic hypogonadism (CHH) is associated with impaired bone mineral density in adulthood, whereas the estimates on bone structure in adolescents with CHH has not been previously evaluated. This study describes bone structure in CHH patients and compares it to that in boys with constitutional delay of growth and puberty (CDGP). Design A cross-sectional study. Methods Peripheral quantitative computed tomography (pQCT) of non-dominant arm and left leg were performed. Volumetric bone mineral density (BMD), bone mineral content, and area in trabecular and cortical bone compartments were evaluated, and bone age-adjusted Z-scores for the bone parameters were determined. Results The participants with CHH had more advanced bone age and were older, taller and heavier than the CDGP boys, yet they had lower trabecular BMD in distal radius (147.7 mg/mm(3) [95% CI, 128-168 mg/mm(3)] vs. 181.2 mg/mm(3) [172-192 mg/mm(3)], p = .002) and distal tibia (167.6 mg/mm(3) [145-190 mg/mm(3)] vs. 207.2 mg/mm(3) [187-227 mg/mm(3)], p = .012), respectively. CHH males had lower cortical thickness at diaphyseal tibia than the participants with CDGP (p = .001). These between-group differences remained significant in corresponding Z-scores adjusted for bone age and height (p = .001). In CDGP group, serum testosterone correlated positively with trabecular BMD (r = 0.51, p = .013) at distal radius, and estradiol levels correlated positively with trabecular BMD at the distal site of tibia (r = 0.58, p = .004). Conclusions Five treatment-naive male patients with CHH exhibited poorer trabecular BMD than untreated males with CDGP. We speculate that timely low-dose sex steroid replacement in CHH males may benefit skeletal health in adulthood.Peer reviewe

Circulating Liver-enriched Antimicrobial Peptide-2 Decreases During Male Puberty

Context: Circulating levels of liver-enriched antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist, decrease under caloric restriction and increase in obesity. The role of LEAP2 in male puberty, a phase with accelerated energy demand, is unclear. Objective: This work aimed to investigate whether circulating LEAP2 levels are downregulated in boys following the onset of puberty to respond to the energy need required for growth. Methods: We determined circulating LEAP2 levels in 28 boys with constitutional delay of growth and puberty (CDGP) who participated in a randomized controlled trial (NCT017977181, and were treated with letrozole (n = 15) or intramuscular low-dose testosterone (T) (n = 13) for 6 months. Blood sampling and dual-energy x-ray absorptiometry-measured body composition were performed at 0-, 6-, and 12-month visits. Results: Serum LEAP2 levels decreased statistically significantly during pubertal progression (0-6 months: mean decrease -4.3 (10.3) ng/mL, P = .036 and 0-12 months: -3.9 19.31 ng/mL, P = .033). Between 0 and 6 months, the changes in serum LEAP2 levels correlated positively with changes in percentage of body fat (r(s) = 0.48, P = .011), and negatively with growth velocity and estradiol levels (r(s) = -0.43, P = .022, r(s) = -0.55, P = .003, respectively). In the T group only, the changes in serum LEAP2 correlated negatively with changes in T and estradiol levels. Between 0 and 12 months, the change in LEAP2 levels correlated negatively with the change in high-density lipoprotein levels (r(s) = -0.44, P = .022) and positively with the change in insulin (r(s) = 0.50, P = .009) and HOMA-IR (r(s )= 0.51, P = .007) levels. Conclusion: Circulating LEAP2 levels decreased after induction of puberty reciprocally with increased growth rate and energy demand, reflecting the metabolic state of the adolescent. Further, the results suggest that estradiol levels may have a permissive role in downregulating circulating LEAP2 levels.Peer reviewe