Insulin Acutely Increases Fibrinogen Production in Individuals With Type 2 Diabetes but Not in Individuals Without Diabetes

Abstract

Fibrinogen is an acute-phase reactant and an independent cardiovascular risk factor. Insulin without amino acid replacement acutely suppressed fibrinogen production in nondiabetic and type 1 diabetic individuals. Fibrinogen production and plasma concentration increase in insulin-resistant type 2 diabetes. It is not known whether altered response to insulin contributes to hyperfibrinogenemia in type 2 diabetes. Fibrinogen fractional (FSR) and absolute (ASR) synthesis rates were measured using a leucine isotopic model in type 2 diabetic men (n ‫؍‬ 7; age ‫؍‬ 51 ؎ 3 years; BMI ‫؍‬ 26.7 ؎ 1 kg/m 2 ) compared with matched nondiabetic subjects under basal conditions and following a 4-h euglycemic-, euaminoacidemic-hyperinsulinemic clamp. Basal fibrinogen concentration (؉35%, P < 0.05) and ASR (؉35%, P < 0.05) were greater in the diabetic subjects. Following clamp, fibrinogen FSR and ASR were unchanged in the control subjects. In contrast, fibrinogen FSR and ASR increased by 41 and 43%, respectively (P < 0.05), in the diabetic subjects. Thus, fibrinogen production is acutely increased by insulin when euglycemia and euaminoacidemia are maintained in type 2 diabetic individuals but not in nondiabetic individuals. Enhanced fibrinogen production by insulin is likely to be a key alteration contributing to hyperfibrinogenemia and therefore cardiovascular risk in type 2 diabetes. Unchanged fibrinogen production in nondiabetic individuals suggests a role of plasma amino acids in regulating fibrinogen production in humans.

Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes

“…That fibrinogen synthesis is increased in type 2 diabetes, even in the absence of micro-or macroalbuminuria, has been previously demonstrated [20,35]. The present study adds to this information, showing that a further increase not only of fibrinogen concentration but also of its synthesis occurs when type 2 diabetes patients are also albuminuric (Table 1) [7,8].…”

“…In the albuminuric, type 2 diabetic patients, both albumin FSR and ASR, as well as fibrinogen FSR, were greater than in either the normo- albuminuric patients or the healthy controls, further confirming the association between albuminuria and the increased rates of these plasma proteins. The mechanism(s) possibly associated with the increased fibrinogen production in type 2 diabetes have been previously discussed in detail [20,21,35], and may include insulin resistance, hyperglucagonaemia, increased fibrinogen degradation products acting as stimulators of fibrinogen production in the liver, and possibly, also a subclinical inflammatory state otherwise not detectable by standard assays. In our albuminuric type 2 diabetes patients, the increased ESR, which is a common finding in albuminuria [36], may indicate the occurrence of a mild inflammatory state, despite the normality of other biochemical (leucocyte counts, urinalysis, α 2 -globulins) and clinical indices of inflammation, with the exception of a mild, albeit insignificant, increase of CRP.…”

Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness

“…This confirmed the well-known association between blood glucose and fibrinogen. 32 In conclusion, this study shows that patients with diabetes and HT have higher arterial stiffness compared to those with one disease or the other. Fasting glucose is the first independent determinant of PWV that may be used as a relevant tool to assess the influence of cardiovascular risk factors on arterial stiffness in high-risk patients.…”

Effect of Low and High Dose Sugammadex on Erythrocyte Deformability in Streptozotocin-Induced Diabetic Rats

“…Anionic charge in cell membranes decreases in diabetes, resulting in erythrocyte aggregation. Erythrocyte aggregation facilitates intra vascular acidosis and plathelet aggregation (13,14).…”

“…Other important pathological changes are alterations in membran lipid ratio, glicolisation in skeletal proteins, alterations in several enzyme functions (10,11). Additionally plasma levels of fibrinogen, albumin change and a tendency towards platelet and erythrocyte aggregation emerges (12)(13)(14). This multifactorial process results in the decreased erythrocyte deformability, which leads to circulation and nutritional impairements.…”