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2.  Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein 
Background
Matrix Gla protein (MGP) is an important inhibitor of calcification. The objective of the present study of patients with type 2 diabetes and normal or slightly altered kidney function was to evaluate levels of inactive, dephospho-uncarboxylated MGP(dp-ucMGP) and total uncarboxylated MGP(t-ucMGP) and assess their links with biological and clinical parameters (including peripheral vascular calcification).
Methods
The DIACART study is a cross-sectional cohort study of 198 patients with type 2 diabetes and normal or slightly altered kidney function. Matrix Gla protein levels were measured with an ELISA and all patients underwent multislice spiral computed tomography scans to score below-knee arterial calcification.
Results
In the study population as a whole, the mean dp-ucMGP and t-ucMGP levels were 627 ± 451 pM and 4868 ± 1613 nM, respectively. Glomerular filtration rate, age and current vitamin K antagonist use were independently associated with dp-ucMGP levels. When the study population was divided according to the median peripheral arterial calcification score, patients with the higher score displayed significantly lower t-ucMGP and significantly higher dp-ucMGP levels. Furthermore, plasma dp-ucMGP was positively associated with the peripheral arterial calcification score (independently of age, gender, previous cardiovascular disease and t-ucMGP levels).
Conclusions
High dp-ucMGP levels were independently associated with below-knee arterial calcification score in patients with type 2 diabetes and normal or slightly altered kidney function. The reversibility of the elevation of dp-ucMGP levels and the latter’s relationship with clinical events merit further investigation.
doi:10.1186/1475-2840-13-85
PMCID: PMC4017083  PMID: 24762216
Matrix gla protein; Type 2 diabetes; Peripheral calcification
3.  SMRT-GPS2 corepressor pathway dysregulation coincides with obesity-linked adipocyte inflammation 
Low-grade chronic inflammation is a major characteristic of obesity and results from deregulated white adipose tissue function. Consequently, there is interest in identifying the underlying regulatory mechanisms and components that drive adipocyte inflammation. Here, we report that expression of the transcriptional corepressor complex subunits GPS2 and SMRT was significantly reduced in obese adipose tissue, inversely correlated to inflammatory status, and was restored upon gastric bypass surgery–induced weight loss in morbid obesity. These alterations correlated with reduced occupancy of the corepressor complex at inflammatory promoters, providing a mechanistic explanation for elevated inflammatory transcription. In support of these correlations, RNAi-mediated depletion of GPS2 and SMRT from cultured human adipocytes promoted derepression of inflammatory transcription and elevation of obesity-associated inflammatory markers, such as IL-6 and MCP-1. Furthermore, we identified a regulatory cascade containing PPARγ and TWIST1 that controlled the expression of GPS2 and SMRT in human adipocytes. These findings were clinically relevant, because treatment of diabetic obese patients with pioglitazone, an antidiabetic and antiinflammatory PPARγ agonist, restored expression of TWIST1, GPS2, and SMRT in adipose tissue. Collectively, our findings identify alterations in a regulatory transcriptional network in adipocytes involving the dysregulation of a specific corepressor complex as among the initiating events promoting adipose tissue inflammation in human obesity.
doi:10.1172/JCI64052
PMCID: PMC3533285  PMID: 23221346
4.  The Charcot Foot in Diabetes 
Diabetes Care  2011;34(9):2123-2129.
The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity.
doi:10.2337/dc11-0844
PMCID: PMC3161273  PMID: 21868781

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