Dissertations

Jani Haukka: Genetic and metabolomic factors of type 1 diabetes and diabetic kidney disease

Type 1 diabetes and its complication, diabetic kidney disease, are severe and complex conditions. Type 1 diabetes affects over 8 million individuals worldwide, while diabetic kidney disease is the leading cause of end-stage kidney disease in developed countries. Although the understanding of the aetiology of type 1 diabetes, as well as the genetic and metabolomic background of diabetic kidney disease, has improved greatly in recent years, much remains unknown.
 
My PhD thesis aimed to study the presence of residual insulin production in individuals with type 1 diabetes, measured by serum C-peptide concentrations, and to investigate genetic and metabolomic background of diabetic kidney disease.
 
Our results showed that a significant proportion of individuals with type 1 diabetes retain C-peptide, and thus insulin production, even years or decades after the diabetes onset. Those with an older age at onset and a lower type 1 diabetes polygenic risk score were more likely to retain C-peptide production. The C-peptide concentrations were also associated with a lower risk of diabetic complications.
 
We also identified serum metabolites associated with increased risk of diabetic kidney disease, including N-trimethyl-5-aminovalerate and the artificial sweetener erythritol. The most significant genetic findings included the LTA gene, which is involved in inflammation regulation, and CCSER1 gene. 

Jani Haukka: Genetic and metabolomic factors of type 1 diabetes and diabetic kidney disease. 2025

Pauliina Repo: Genetic predisposition to uveal melanoma in the Finnish population

This thesis explored genetic factors that may contribute to the risk of developing uveal melanoma (UM), the most common eye cancer in adults, with a focus on the Finnish population, where uveal melanoma incidence is among the highest in the world. 

Particular attention was given to the BAP1 gene, a known uveal melanoma risk gene. The study confirmed that ~2% of all patients and 25% of those with familial uveal melanoma carried pathogenic BAP1 variants, including two potential Finnish founder mutations. 

Other known cancer risk genes – such as BRCA1, MET, CHEK2, DDX41, FANCM, HOXB13, RAD50, SDHA, and SDHB – were occasionally found to harbor pathogenic or likely pathogenic variants. However, no strong evidence supported the involvement of the MBD4 gene, another suggested uveal melanoma risk gene, in uveal melanoma predisposition in the Finnish population. 

Overall, the study highlights the importance of BAP1 and expands the possibility that uveal melanoma may be part of broader cancer syndromes in some individuals.

Pauliina Repo: Genetic predisposition to uveal melanoma in the Finnish population. 2025

Rishi Banerjee: Novel disease mechanisms and effects of gene therapy in mouse models of neonatal mitochondrial complex III deficiency

GRACILE syndrome is a severe genetic disease affecting newborns. The disease disrupts the body's ability to produce energy, affecting multiple organs and early death. 

This study focused on using gene therapy, a technique that introduces healthy copies of genes into cells to fix problems. In experiments with mice that have GRACILE syndrome, researchers found that targeting the liver with gene therapy could dramatically improve the animals' health. The treated mice lived longer, maintained normal body temperatures, and had better control over their blood sugar levels.

One surprising finding was the role of the liver in regulating body temperature. Normally, tissues like brown fat and muscle help keep the body warm, but in the sick mice, these tissues weren't working properly. After gene therapy, the liver metabolism was able to produce enough heat to keep the mice warm, showing that fixing the energy production of the liver can compensate when other systems fail. 

This research offers hope for future treatments of GRACILE syndrome and similar mitochondrial diseases, suggesting that even if only one organ can be treated, significant health improvements are possible. 

Rishi Banerjee: Novel disease mechanisms and effects of gene therapy in mouse models of neonatal mitochondrial complex III deficiency. 2025.

Marika Eriksson: Cerebral small vessel disease and stroke in type 1 diabetes – The impact of blood pressure, haptoglobin genotype, and diabetic retinopathy

Cerebrovascular disease, such as stroke, is a severe complication of type 1 diabetes, with a high risk of disability and mortality. It is not fully clear how cerebrovascular complications develop, but diabetes is suggested to damage the brain’s small vessels similarly to other diabetic microvascular damage.
 
This study aimed to assess factors associated with early signs of cerebrovascular brain damage in asymptomatic individuals with type 1 diabetes, as well as risk markers for the development of stroke in these individuals.
 
Our results showed that cerebral small vessel disease is associated with elevated nocturnal blood pressure in type 1 diabetes. We also found cerebral small vessel diseases to be more common with increasing severity of diabetic eye disease and that severe diabetic eye disease marked an increased risk of having a stroke. 

The results suggest that cerebrovascular disease in type 1 diabetes is linked to microvascular damage and that the health of the eye’s blood vessels may reflect the health of the brain’s blood vessels.

Marika Eriksson: Cerebral small vessel disease and stroke in type 1 diabetes – The impact of blood pressure, haptoglobin genotype, and diabetic retinopathy. 2025.

Anna Abdollahi: Sleep habits of Finnish preschoolers: Associations with diet and weight

Having a later chronotype often increases the risk of circadian misalignment, as social demands often conflict with internal biological clocks. Among adolescents and adults, a later chronotype has been associated with less healthy sleep patterns, poorer diet quality, increased weight status, and reduced overall well-being. However, little research has focused on younger children, leaving it unclear when these associations begin to develop.

Using data from the DAGIS project, we employed novel, data-driven sleep estimation methods with actigraphy data to assess several sleep measures, including chronotype.

While children with a later chronotype were not associated with higher weight outcomes during preschool age, they were associated with less healthy diet quality, including lower vegetable and higher sugary food consumption. Furthermore, children with a later chronotype at preschool age were associated with greater weight gain over the eight-year follow-up period.

In conclusion, our findings suggest that preschool age may be a critical period when children vulnerable to circadian misalignment potentially begin to experience its negative effects. More research is needed to understand sleep, diet, and weight trajectories in children and the early role of circadian misalignment in weight development.

My dissertation also explored the associations between other sleep measures (duration, timing, quality) with diet (energy intake, macronutrient intake, and food consumption), and weight outcomes.

Anna Abdollahi: Sleep habits of Finnish preschoolers: Associations with diet and weight. 2025.

Jenni Ikonen: Frailty and functioning as determinants of healthcare use

The aging global population is creating new demands for healthcare systems. Understanding factors that drive healthcare use is essential for planning preventative measures and adapting the services to meet the needs of the aging populations. Frailty, characterized by vulnerability to stressors and impaired recovery, is proposed to explain health differences among older adults, while maintaining functioning is central to healthy aging. Therefore, we aimed to investigate whether frailty and functioning would be associated with healthcare use.

We found that frailty was associated with greater specialized and primary healthcare service use. Furthermore, frailty and its faster progression rate were associated with increased medical imaging service use and costs. Participants with poorer physical functioning had higher utilization rates of specialized healthcare services compared to participants with better functioning. Poorer mental functioning, in turn, was associated with a higher number of first outpatient visits. In conclusion, public health interventions should be considered to prevent frailty and support functioning among aging populations.

Jenni Ikonen: Frailty and functioning as determinants of healthcare use. 2024.

Natalia Hetemäki: Estrogen biosynthesis in subcutaneous and visceral adipose tissue in women 

Adipose tissue, or fat tissue, is important in the production of sex steroids like estrogens and androgens, especially after menopause. The distribution of adipose tissue in women changes over the course of their reproductive life – at menopause, the relative amount of visceral compared to subcutaneous adipose tissue increases, and this leads to an increased risk of metabolic disorders such as cardiovascular disease and type of 2 diabetes. Menopausal hormone therapy seems to mitigate these changes.

We studied changes taking place in the biosynthesis of estrogens in subcutaneous and visceral adipose tissue in women before and after menopause. We also studied how the production of estrogens and androgens in fat is affected by the use of menopausal hormone therapy.

We found that considerable amounts of estrogens were produced in fat already before menopause. After menopause, the role of visceral adipose tissue in the production of estrogens was highlighted. Users of menopausal hormone therapy had high tissue to serum concentrations of estrogens and increased local estrogen-to-androgen ratios in adipose tissue compared to women without hormone therapy. These changes could play a role in the preventive effect that menopausal hormone therapy has on menopause-associated visceral adiposity.

Natalia Hetemäki: Estrogen biosynthesis in subcutaneous and visceral adipose tissue in women. 2024.