Maturity-Onset Diabetes of the Young, Type 4

In this study, the investigators aim to find a biomarker of Parkinson's disease. This is done using imaging scans called Positron Emission tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Magnetic Resonance Imaging (MRI). The findings will provide a deeper understanding of the brain changes in Parkinson's disease. More importantly, this study will help with the discovery and development of new medications aiming to delay progression of PD symptoms.

Diabetes is a disorder of energy energy metabolism. Glucose is the main energy substrate for generation of ATP to maintain cellular metabolism, structure and function. Glucokinase (GK) serves as a glucose sensor for the initiation of the energy generation.for energy metabolism. Dorzagliatin is a novel, first-in-class, dual-acting allosteric GK activator (GKA). It increases the affinity of GK for glucose by directly binding a pocket distal to its active site, thus lowering the set point for glucose-stimulated insulin secretion in the beta-cell.
Dorzagliatin is a new drug which acts as GK sensor activator (GKA). It can restore the sensitivity of the pancreas cells to glucose and improve glucose control. The drug has been trialled in healthy volunteers and in individuals with type 2 diabetes.
The aim of this study is to understand the way in which dorzagliatin works to improve blood sugar control in people with diabetes. The study will look at how dorzagliatin affects insulin secretion and the sensitivity of the pancreas to changes in blood sugar levels. We will examine whether dorzagliatin can restore the function of this GK sensor in patients with known mutations. In a cross-over study, we will evaluate the effects of dorzagliatin, a specific GKA versus placebo in terms of insulin secretion and beta-cell glucose sensitivity in patients with newly-diagnosed T2D and patients who are known heterozygous carriers of GK mutations.

Monogenic diabetes accounts for 1-2% of diabetes cases, although it is often misdiagnosed as either type 1 diabetes or type 2 diabetes. Knowledge of the genetic etiology of diabetes enables more appropriate treatment, better prediction of disease progression, screening of family members and genetic counseling. These monogenic diabetes result from gene mutations that reduce beta-cell function. To date, about 20 genes involved in insulin-secretion pathway hav been identified; they correspond to a broad of two main clinical conditions [neonatal diabetes mellitus (NDM) and Maturity-Onset Diabetes of the Young (MODY)]. However, it still remains subtypes of monogenic diabetes that are unelucidated. The investigators project focus on families with a clinical and familial history highly suggesting a MODY diabetes but without genetic etiology. The investigators objective is to set up a collection of families with at least three family members presenting a MODY diabetes.