Tyypin 2 diabeteksen ja siihen liittyvien ominaisuuksien periytyvyys

Disturbances in insulin sensitivity and insulin secretion precede the manifestation of type 2 diabetes. Both genes and environment contribute to the diabetes risk. Heritability indicates the proportion to which genotype determines the variability of a trait, such as for example blood glucose concentration. The current work was done for the Hjelt institute and for the Finnish institute of Molecular Medicine (FiMM) in the University of Helsinki. Heritability of insulin sensitivity, insulin secretion and traits associated with type 2 diabetes were estimated by means of twin and family studies. The twins belonged to the Finnish Twin Cohort Study of the University of Helsinki and the families participated in the Botnia study, a project on type 2 diabetes genetics. The collecting of the material was made between the years 1992 - 2004. Insulin sensitivity was measured by means of hyperinsulinaemic euglycaemic clamp technique. Insulin secretion was measured both via oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. The heritability of body mass index (BMI) and type 2 diabetes were estimated in a follow-up study of twins. Furthermore, heritability estimates of several glucose metabolism and insulin sensitivity related traits were obtained by examining Botnia study families where at least two family members had type 2 diabetes. Altogether 66 monozygotic (MZ) and 85 dizygotic (DZ) twin pairs underwent OGTT. A subset of the pairs participated also in IVGTT- and clamp studies. The follow-up study was based on information that was received from 10400 twin pairs during a maximum of 28 years of follow-up. From the Botnia-study, 5810 adults from 942 families were chosen: 1707 of them had type 2 diabetes. The average family size was 6,17. On the basis of the metabolic studies, it was concluded that the genotype determines the insulin secretion's early phase, which begins immediately after the ingestion or infusion of glucose. The heritability of this trait varied between 55% and 76%. The majority of variation in insulin sensitivity, instead, seemed to be due to non-hereditary factors, as the heritability of insulin sensitivity was only 37%. In the follow-up study, 6.3% of male and 5.1% of female twins got type 2 diabetes. BMI calculated on the basis of the data recorded at the start of the follow-up, predicted future diabetes well. On average, the hazard ratio for type 2 diabetes was 1,22 per each BMI unit and the risk began to increase already from the BMI-value of 20kg/m2. The hazard ratios for type 2 diabetes in normal weight, overweight, obese and morbidly obese twins were 0.59, 2.96, 6.80 and 13.64, respectively. When BMI and type 2 diabetes were modelled together, the heritability of BMI in men was 75%, and 71% in women. Correspondingly, the heritability of type 2 diabetes was 73% in men and 64% in women, respectively. The genetic factors influencing BMI explained only 16% of the risk for type 2 diabetes among men and 21% of the risk among women. In the Botnia study, the highest heritability estimate for type 2 diabetes, 69%, was observed among individuals aged 35 to 60 years. The heritability of the early phase of insulin secretion varied between 41% (all subjects) and 50% (non-diabetic subjects). The heritability of insulin sensitivity was the same as among twins, from 37% to 40%. Among diabetes-related traits, the highest heritability estimates were obtained for lean body mass (53% to 65%), serum HDL cholesterol concentration (52% to 61%) and suppression of free fatty acids during OGTT (63% to 76%). The variation of all insulin sensitivity and insulin secretion -related traits were smaller within than between families. It is stated as a summary of this doctoral thesis that the risk for type 2 diabetes seems to be an inherited trait. A relatively small share in this risk, on the other hand, seems to be due to genes which influence BMI. Finally, the early phase of the pancreatic insulin secretion appears to be an aspect of metabolism that encompasses promising phenotypes for genomic studies.Häiriöt sokeriaineenvaihdunnan insuliiniherkkyydessä ja insuliininerityksessä edeltävät tyypin 2 diabeteksen puhkeamista. Sekä perimä (geneettiset tekijät) että elintavat vaikuttavat diabetesriskiin. Periytyvyys eli heritabiliteetti ilmaisee, paljonko perimä määrää mitattavan ominaisuuden kuten esimerkiksi verensokerin vaihtelua. Helsingin yliopiston lääketieteellisen tiedekunnan alaisessa, Hjelt-instituutille ja Suomen molekyylilääketieteen instituutille (FiMM) tehdyssä väitöstutkimuksessa selvitettiin sokeriaineenaihdunnan, insuliininerityksen ja diabetesriskin periytyvyyttä kaksos- ja perhetutkimuksen keinoin. Kaksoset kuuluivat Helsingin yliopiston Kaksostutkimukseen, joka vuonna 2014 täyttää 40 vuotta. Perheaineisto koottiin suomalaisesta Botnia-tutkimuksesta, joka on maailman huomattavimpia tyypin 2 diabeteksen perimää selvittäviä projekteja. Aineiston kokoaminen ja seuranta tehtiin vuosien 1992 - 2004 aikana. Tutkimuksessa määritettiin insuliiniherkkyys clamp-tekniikan avulla: tutkittavan henkilön veren insuliinitaso nostettiin keinotekoisesti halutulle tasolle ja katsottiin, kuinka paljon sokeriliuosta on annettava laskimoon estämään insuliinin aikaansaama verensokerin lasku. Insuliinineritys mitattiin sekä tavallista (oraalista, OGTT) että laskimonsisäistä (IVGTT) sokerirasitusta käyttäen. Tyypin 2 diabeteksen ja kehon painoindeksin (BMI) periytyvyys selvitettiin pitkässä seurantatutkimuksessa. Lisäksi useille sokeriaineenvaihduntaan ja insuliiniherkkyyteen liittyville piirteille määritettiin periytyvyys tutkimalla Botnia-tutkimukseen osallistuneita perheitä, joissa vähintään kahdella perheenjäsenellä on tyypin 2 diabetes. Kaikkian 66 identtiselle ja 85 epäidenttiselle kaksosparille tehtiin OGTT ja osalle lisäksi sekä IVGTT että clamp. Seurantatutkimus perustui 10400 kaksosparista saatuihin tietoihin. Pisin seuranta-aika oli 28 vuotta. Botnia-tutkimuksesta valittiin 942 perhettä, joihin kuului 5810 aikuista. Heistä 1707:llä oli tyypin 2 diabetes. Keskimääräinen perhekoko oli 6,17. Kaksosille tehtyjen aineenvaihduntatutkimusten perusteella ilmeni, että perimä määrää vahvasti erityisesti insuliininerityksen varhaista vaihetta, joka alkaa välittömästi sokerin nauttimisen tai laskimoon annostelun jälkeen. Tämän ominaisuuden periytyvyys vaihteli 55 ja 76% välillä. Valtaosa insuliiniherkkyyden vaihtelusta sen sijaan näytti johtuvan ei-perinnöllisistä syistä ja insuliiniherkkyyden periytyvyydeksi saatiin vain 37%. Seurantatutkimuksessa 6,3% mies- ja 5,1% naiskaksosista sairastui tyypin 2 diabetekseen. Seurannan alussa kerättyjen tietojen perusteella laskettu painoindeksi ennusti tulevaa diabetesta erittäin hyvin. Keskimäärin riskisuhde oli 1,22 jokaista nousevaa BMI-yksikköä kohti. Diabetesriski alkoi lisääntyä jo BMI-arvosta 20 kg/m2 lähtien. Normaalipainoisten, ylipainoisten, lihavien ja sairaalloisen lihavien riskisuhteet olivat 0,59, 2,96, 6,80 ja 13,64. Kun sekä BMI että tyypin 2 diabetes huomioitiin yhtä aikaa, saatiin BMI:n periytyvyydeksi 75% miehillä ja 71% naisilla. Vastaavasti tyypin 2 diabeteksen periytyvyydeksi saatiin miehillä 73% ja naisilla 64%. Painoindeksin perintötekijät selittivät vain 16% miesten ja 21% naisten riskistä sairastua tyypin 2 diabetekseen. Botniatutkimuksessa tyypin 2 diabeteksen periytyvyys oli suurimmillaan 69 prosenttia, 35 - 60 -vuotiaiden keskuudessa. Insuliininerityksen varhaisen vaiheen periytyvyys vaihteli 41% (kaikki tutkittavat) ja 50% (tutkittavat, joilla ei diabetesta) välillä. Insuliiniherkkyyden periytyvyys oli sama kuin kaksostutkimuksessa, 37-40%. Diabetekseen liittyvistä aineenvaihdunnan ominaisuuksista korkein periytyvyys saatiin kehon rasvattomalle massalle (53-65%), seerumin HDL-kolesteroli-pitoisuudelle (52-61%) ja OGTT:n aikaiselle vapaiden rasvahappojen pitoisuuden laskulle (63-76%). Kaikkien insuliiniherkkyyteen ja insuliinineritykseen liittyvien ominaisuuksien vaihtelu perheiden sisällä oli pienempää kuin perheiden välillä. Väitöstutkimuksen yhteenvetona todetaan, että riski sairastua tyypin 2 diabetekseen on periytyvä. Painoindeksiin vaikuttavilla geeneillä on merkittävä, kenties tähän asti oletettua pienempi osuus tässä riskissä. Lisäksi todetaan, että insuliininerityksen varhainen vaihe kannattaa huomioida haettaessa tyypin 2 diabetekselle altistavia perintötekijöitä esimerkiksi koko genomin laajuisissa assosiaatiotutukimuksissa

Jännitysnäytelmä laboratoriossa - osa 1 : mitä todella tapahtui hellekesänä 1921?

Insuliini 100 vuotta. Koko artikkeli lyhentämättömänä kirjallisuusluetteloineen löytyy osoitteesta www.diabetes.fi/aineistoj

Jännitysnäytelmä laboratoriossa - osa 2 : läpimurto lähestyy, tunteet kuumenevat

Insuliini 100 vuotta. Lue koko artikkeli lyhentämättömänä ja kirjallisuus- katsauksineen: www.diabetes.fi/aineistoja

Onnentoivotuksia ja yhdyskäytäviä

Yhteistyö on opettanut minulle lääkärinä nöyryyttä

The Impact of Nutrition Education Intervention with and Without a Mobile Phone Application on Nutrition Knowledge Among Young Endurance Athletes

Athletes often have significant gaps in their nutrition knowledge. Thus, the aim of this study was to investigate whether young Finnish endurance athletes’ nutrition knowledge and dietary intake can be improved through an education intervention with or without a mobile food application. Seventy-nine endurance athletes, 18.0 years (SD: 1.4), participated in this randomized, controlled intervention. We compared the effects of participatory nutrition education sessions alone (group EDU) to those including the use of a mobile food application (group EDU + APP) for four days after each session. Both groups attended three 90-min education sessions fortnightly. The participants completed a validated nutrition knowledge questionnaire in Weeks 0, 5, and 17, and a three-day food diary in Weeks 0 and 17. The education plan was based on the Self-Determination Theory and the concept of meaningful learning process. The EDU group’s nutrition knowledge scores were: 78 (week 0), 85 (week 5), and 84 (week 17) and the EDU + APP group’s 78, 86, and 85, respectively. Nutrition knowledge increased significantly (main effect of time (p 0.05). The amount of carbohydrates was below endurance athletes’ recommendations throughout the intervention. The reported energy intakes were also below the estimated energy expenditures. In conclusion, nutrition knowledge improved significantly after only three education sessions and food diary feedback, but the mobile app did not improve learning further. However, the nutrition education intervention alone was not enough to change dietary intake

Napping and the risk of type 2 diabetes: a population-based prospective study

OBJECTIVE: Some studies indicate an association between napping and increased risk of type 2 diabetes. We studied this prospectively in a sample representative of general population. METHODS: A questionnaire was administered to the Finnish Twin Cohort in 1990 (response rate 77%, age 33-60 years). The study population included 12,244 subjects who replied to the question "Do you sleep during the daytime (take naps)?" with five response alternatives ranging from "no need" to "every or almost every day." Information on incident cases of diabetes was obtained by linkage to nationwide registers. Logistic regression models were used to obtain odds ratios (ORs) (95% confidence intervals) for incident type 2 diabetes risk in 1991-2004 by napping category. Adjustments were made for 11 socio-demographic and lifestyle covariates. For subjects aged 33-45 years at baseline, a questionnaire in 2011 provided information on prevalent diabetes. RESULTS: Thirty-four per cent had no need for napping, and 15% did so on ≥3 days weekly. There were 356 incident type 2 diabetes cases during the follow-up. Using the 'no need' category as the reference, the risk of type 2 diabetes was significantly increased only among those napping most frequently [OR 1.86 (1.29-2.67), age- and sex-adjusted]. After adjusting for other covariates, the results were essentially the same, but when adjusted for body mass index, the association decreased (to about 1.3) and was statistically non-significant. Analysis of 2011 self-reported type 2 diabetes was in line with the register data. CONCLUSIONS: Frequent napping is associated with future risk of type 2 diabetes. This association is largely explained by obesity.Peer reviewe

Replacing Animal-Based Proteins with Plant-Based Proteins Changes the Composition of a Whole Nordic Diet-A Randomised Clinical Trial in Healthy Finnish Adults

Increased consumption of plant-based foods and decreased consumption of animal-based foods is recommended for healthy diets and sustainable food production. We investigated the effects of partial replacement of dietary animal proteins with plant-based ones on intake of energy-yielding nutrients, fibre, and plasma lipoproteins. This 12-week randomised clinical intervention comprised 107 women and 29 men (20-69 years) in three diet groups with different dietary protein compositions ("ANIMAL": Animal 70%/plant 30%; "50/50": Animal 50%/plant 50%; "PLANT": Animal 30%/plant 70%; all: Protein intake 17 E%). Nutrient intakes were assessed by 4-day food records. Saturated fat intake (E%) was lower and polyunsaturated fatty acid intake (E%) higher in the PLANT and 50/50 groups compared to the ANIMAL group (p 0.05). Replacing animal protein with plant protein sources in the diet led to an increased fibre intake and improved dietary fat quality as well as blood lipoprotein profile. Flexitarian diets could provide healthy and more sustainable alternatives for the current, predominantly animal-based diets.Peer reviewe