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At least 19 recordsLinked to original sources
PubMed2026

Management of complex lipid disorders in a community lipid clinic setting: Implementing a multidisciplinary model.

BACKGROUND: Large treatment gaps exist in the management of lipid disorders, and many high-risk patients have factors that complicate management efforts. While lipid clinics exist within academic medical centers, most of these patients are cared for in community settings. OBJECTIVE: To report our experience and results managing challenging and complex lipid disorders in a community-based lipid clinic. METHODS: We established a specialized lipid clinic in a community medical setting, with a focus on patients with management challenges and/or suspicion of a genetic lipid disorder, employing a multidisciplinary approach to optimize patient outcomes, emphasizing appropriate medical therapies and lipid genetic testing in selected patients. Retrospective electronic health record data were collected to analyze patient characteristics, treatment patterns, and lipid results. RESULTS: Over the period 2022 through 2024, 183 patients were seen (mean 63 years, 62% female). The challenging nature of the patient population was highlighted by high rates of statin intolerance (50%), no lipid medical therapy at baseline (50%), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], diabetes, and/or hypertension-61%). Despite this, over a mean follow-up of 9.4&#xa0;&#xb1;&#xa0;7.3 months, we observed a mean low-density lipoprotein cholesterol&#xa0;decrease of 49&#xa0;mg/dL (-24.5%, P&#xa0;<&#xa0;.001), along with significant decreases in total cholesterol and triglycerides. Pathogenic dyslipidemia genetic variants were discovered in 21 patients (of 105 tested). Significant lipid improvements in the whole cohort, as well as multiple subgroups, were associated with greater utilization of combination therapies. CONCLUSION: Patients with complex lipid disorders can be successfully managed within a specialized lipid clinic in community medical settings. Applying such a multidisciplinary model outside of traditional academic medical centers offers the potential to raise the level of lipid management and ASCVD prevention more broadly in larger populations.

Combination medical therapy↗
PubMed2025

Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: Novel cases of familial chylomicronemia syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

PURPOSE: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases. METHODS: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing. Preliminary variant pathogenicity criteria and classification, based on the American College of Medical Genetics and Genomics guidelines, were obtained online and verified. Phenotype evaluation was based on lipoprotein lipase activity deficiency, a clinical score, and/or type I hyperlipoproteinemia determined in 25 patients. RESULTS: Twenty-four biallelic variants were analyzed. Evidence-based criteria allowed the reclassification of 8 likely pathogenic (LP) variants in the LPL, APOA5, and LMF1 genes into pathogenic (P) and the change of 2 variants of uncertain significance (VUS) to LP. Conversely, 2 variations in LMF1 remained as VUS. Additionally, 1 variant in LPL and 2 in GPIHBP1 were likely benign. Twenty FCS cases had biallelic P/LP variants and 1 patient, with an FCS phenotype, harbored biallelic VUS. FCS was excluded from 4 patients with pathogenic/likely benign combinations. CONCLUSION: The analysis of the clinical and biochemical features of patients with variants in the FCS canonical genes allowed a confident variant classification that helped in the diagnosis of novel FCS cases.

Humans↗
PubMed1999

Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial combined hyperlipidemia.

There is growing evidence of the capacity of vitamin A to regulate the expression of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This region in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined hyperlipidemia (FCHL). The hypothesis tested here was whether vitamin A (retinol), by controlling the expression of the AI-CIII-AIV gene cluster, plays a role in modulating the hyperlipidemic phenotype in FCHL. We approached the subject by studying three genetic variants of this region: a C1100-T transition in exon 3 of the apoC-III gene, a G3206-T transversion in exon 4 of the apoC-III gene, and a G-75-A substitution in the promoter region of the apoA-I gene. The association between plasma vitamin A concentrations and differences in the plasma concentrations of apolipoproteins A-I and C-III based on the different genotypes was assessed in 48 FCHL patients and 74 of their normolipidemic relatives. The results indicated that the subjects carrying genetic variants associated with increased concentrations of apoA-I and C-III (C1100-T and G-75-A) also presented increased plasma concentrations of vitamin A. This was only observed among the FCHL patients, which suggested that certain characteristics of these patients contributed to this association. The G3206-T was not associated with changes in either apolipoprotein concentrations or in vitamin A. In summary, we report a relationship between genetically determined elevations of proteins of the AI-CIII-AIV gene cluster and vitamin A in FCHL patients. More studies will be needed to confirm that vitamin A plays a role in FCHL which might also be important for its potential application to therapeutical approaches.

Adult↗
PubMed2005

Rare variant of apolipoprotein E (Arg136 -->Ser) in two normolipidemic individuals.

Through the analysis of the common apolipoprotein (apo) E gene polymorphism in large Caucasian population study with the PCR and subsequent restriction analysis, we have identified carriers of mutant allele Arg136-->Ser. Both of them (71-years-old female and her 43-years-old son) have normal lipid parameters. We suggest that Arg136-->Ser mutation in apoE is not necessarily connected with elevated lipid levels in all cases. Furthermore, so far unidentified factors (environmental and/or genetic) are important for the development of lipid metabolism disorders in apoE Arg136-->Ser mutation carriers.

Adult↗
PubMed2005

Combination of circulating antilipoprotein lipase (Anti-LPL) antibody and heterozygous S172 fsX179 mutation of LPL gene leading to chronic hyperchylomicronemia.

CONTEXT: Sporadic hyperchylomicronemia (type V hyperlipoproteinemia) results from complex interactions between genetic and environmental factors that often remain unknown. DESIGN: Upon investigation of a patient suffering from recurrent hypertriglyceridemic pancreatitis without family history or conventional secondary cause of dyslipidemia, we identified a previously unreported nonsense heterozygous lipoprotein lipase (LPL) gene mutation S172fsX179 associated with an antihuman LPL IgG. RESULTS: This autoantibody partially inhibited wild-type LPL activity in vitro. Furthermore, the patient's plasma triglyceride concentrations were efficiently decreased under immunosuppressive treatment, and this was confirmed by sequential withdrawal/reintroduction tests. CONCLUSIONS: We consider that this unique combination of a genetic defect and an autoimmune disease results in chronic major hypertriglyceridemia. Because immunosuppressive treatment can improve this dyslipidemia, assessment of anti-LPL autoantibody is worthwhile in unmanageable chronic major hypertriglyceridemia, even in the presence of a heterozygous LPL deficiency.

Autoantibodies↗
PubMed2006

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

BACKGROUND: Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. AIM: The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. METHODS: We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. RESULTS: We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. CONCLUSION: To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.

Adiponectin↗
PubMed2000

Hereditary dyslipidemias and combined risk factors in children with a family history of premature coronary artery disease.

AIM: Schoolchildren aged 10-11 with a family history of premature coronary artery disease (CAD), were examined in order to identify children with genetically determined dyslipidemias and a combination of risk factors. METHODS: A total of 4000 questionnaires were distributed by the school; 55% of the families answered and returned the questionnaire. Blood lipids, apolipoprotein B, and Lp(a) lipoprotein were analysed in high risk children and their parents. RESULTS: A family history of premature CAD in parents or grandparents was identified in 208 families; 175 agreed to take part in a clinical examination and laboratory tests. Normal blood lipid tests were found in 89 children. Another 48 had an isolated increase of Lp(a) lipoprotein of minor clinical importance. Of the remaining 38 children, 23 had non-hereditary abnormalities of low (LDL) or high density lipoprotein (HDL) cholesterol or apolipoprotein B. Fifteen children were suspected to have genetically determined dyslipidemias or a combination of risk factors: in four, possible familial hypercholesterolaemia (FH); in five, possible familial combined hyperlipidaemia; in three, hereditary low HDL cholesterol; and in three a combination of high LDL cholesterol and Lp(a) lipoprotein concentrations. In addition, possible FH was detected in eight of the parents. CONCLUSION: It is worthwhile asking parents about the occurrence of premature CAD among their child's closest relatives.

Apolipoproteins↗
PubMed2005

Oxidative stress--mediated alterations in glucose dynamics in a genetic animal model of type II diabetes.

Insulin resistance, characterized by an inexorable decline in skeletal muscle glucose utilization and/or an excessive hepatic glucose production, constitutes a major pathogenic importance in a cluster of clinical disorders including diabetes mellitus, hypertension, dyslipidemia, central obesity and coronary artery disease. A novel concept suggests that heightened state of oxidative stress during diabetes contributes, at least in part, to the development of insulin resistance. Several key predictions of this premise were subjected to experimental testing using Goto-Kakizaki (GK) rats as a genetic animal model for non-obese type II diabetes. Euglycemic-hyperinsulinemic clamp studies with an insulin infusion index of 5 mU/kg bw/min were used to measure endogenous glucose production (EGP), glucose infusion rate (GIR), glucose disposal rate (GDR) and skeletal muscle glucose utilization index (GUI). Moreover, the status of oxidative stress as reflected by the urinary levels of isoprostane and protein carbonyl formation were also assessed as a function of diabetes. Post-absorptive basal EGP and circulating levels of insulin, glucose and free fatty acid (FFA) were elevated in GK rats, compared to their corresponding control values. In contrast, steady state GIR and GDR of the hyperglycemic/hyperinsulinemic animals were reduced, concomitantly with impaired insulin's ability to suppress EGP. Insulin stimulated [3H]-2-deoxyglucose (2-DG) uptake (a measure of glucose transport activity) by various types of skeletal muscle fibers both in vivo and in vitro (isolated muscle, cultured myoblasts) was diminished in diabetic GK rats. This diabetes-related suppression of skeletal muscle glucose utilization was associated with a decrease in insulin's ability to promote the phosphorylation of tyrosine residues of insulin receptor substrate-1 (IRS-1). Similarly, the translocation of GLUT-4 from intracellular compartment to plasma membrane in response to insulin was also reduced in these animals. Oxidative stress-based markers (e.g. urinary isoprostane, carbonyl-bound proteins) were elevated as a function of diabetes. Nullification of the heightened state of oxidative stress in the GK rats with alpha-lipoic acid resulted in a partial amelioration of the diabetes-related impairment of the in vivo and in vitro insulin actions. Collectively, the above data suggest that 1) insulin resistance in GK rats occurs at the hepatic and skeletal muscle levels, 2) muscle cell glucose transport exhibited a blunted response to insulin and it is associated with a major defect in key molecules of both GLUT-4 trafficking and insulin signaling pathways, 3) skeletal muscle insulin resistance in GK rats appears to be of genetic origin and not merely related to a paracrine or autocrine effect, since this phenomenon is also observed in cultured myoblasts over several passages and finally heightened state of oxidative stress may mediate the development of insulin resistance during diabetes.

Animals↗
PubMedDate not supplied

Determinants of microalbuminuria in diabetics.

Several risk factors for the development of microalbuminuria such as: blood glucose unbalance, high blood pressure, dyslipidemia, genetic susceptibility have been described and discussed. The object of this study was to ascertain the importance of these factors. To this end albuminuria was measured using MICRAL-test in two groups of subjects: 100 diabetics (43 type I (insulin-dependent) and 57 type II (non insulin-dependent), and 54 controls. According to diabetes duration, the cases were divided into four sub-groups (less than 5 years; 5-9 yrs; 10-19 yrs; over 20 yrs). The mean values of albuminuria were assessed in the two groups (diabetics and controls) and also for each subgroup of diabetes duration. It was found that in insulin-dependent diabetes mellitus (IDDM), the duration of the disease is an important determinant of albuminuria, a significant increase in its values being observed after 10 yrs of diabetes evolution. The importance of diabetes duration, glucose unbalance and high blood pressure (BP) as possible determinants of microalbuminuria was assessed by comparing the micro- and normoalbuminuric diabetics. Our results are similar to those reported by many other authors, showing that these are important risk factors for microalbuminuria, especially in IDDM.

Adult↗
PubMed2005

Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS). OBJECTIVE: To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance. METHODS: The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events. RESULTS: PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin. CONCLUSIONS: Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

Adult↗
PubMed2005

Low density lipoprotein--receptor (LDL-R) gene mutations among Filipinos with familial hypercholesterolemia.

BACKGROUND: Familial Hypercholesterolemia (FH) is an autosomal dominant disease resulting from mutations of the LDL (LDLR) receptor gene leading to a diminished catabolism and elevated level of LDL cholesterol (LDL-C). It is associated with an increased risk for cardiovascular disease (CVD). The MEDPED (Make Early Diagnosis-Prevent Early Death) program, an initiative cited by the WHO Human Genetics Programme in their report on FH, initiated international collaboration to identify and follow-up patients with FH globally. From Asia-Pacific, only 6 countries are participating and no data among Filipinos particularly on genetic profiles is available at present. This study attempts to initiate data collection and participation in the global initiative. OBJECTIVES: Primary: 1. To describe the phenotype of Filipino patients with FH. 2. To determine and characterize the LDL-R gene mutations among Filipino patients with clinical features of FH. Secondary: To determine the association of the clinical characteristics of FH with the presence of LDLR gene mutations. DESIGN: Cross- Sectional Study. SETTING: Multicenter, Outpatient Clinic. PARTICIPANTS: 60 unrelated patients, 18 y/o and above from UP-PGH, Manila Doctors Hospital and Cardinal Santos Medical Center. FH was diagnosed according to the Dutch Lipid Clinic Network Criteria cited by WHO which is based on a history of premature CVD, family history, tendon xanthoma, arcus cornealis, and LDL C levels. METHODS: With informed consent, clinical history, physical examination and lipid profile data were determined. Blood samples were extracted, processed to isolate DNA specimens at the National Institutes of Health, Institute of Human Genetics, and sent to Canterbury Health Laboratories at Christchurch, New Zealand for DNA analysis. ANALYSIS: Descriptive statistics, Fisher's exact test and Student's t-test using Stata version 6.0 software. RESULTS: Sixty patients with a mean age of 55 y/o were included, including 39 (65%) females. The mean LDL level was 227 mg/dl. Cardiovascular Disease and a family history of dyslipidemia were present in 55 & 60% of the samples, respectively. Twenty percent had documented LDL-R gene mutations. Six of the mutations were considered novel. A family history of dyslipidemia, an elevated LDL-C level, and a high FH score exhibited a statistically significant association with mutations. The study population has a high prevalence of CVD at an average age of 55 years with a strong family history of dyslipidemia and very high average LDL-C levels. One out of every 5 patients had LDL-R gene mutations, 6 of which were considered novel. LDL-R gene mutation was significantly associated with family history of dyslipidemia, LDL-C Level and FH score. CLINICAL AND RESEARCH IMPLICATION: This is the first international collaborative genetic study among Filipinos with FH. Data could allow the country to participate in the WHO/MEDPED global program. Collaborative efforts will lead to more effective detection, treatment and prevention of CV events. Novel mutations were discovered and further analysis of these genes will be done.

Adult↗
PubMedDate not supplied

Paraoxonase gene polymorphism and serum activity in progressive IgA nephropathy.

BACKGROUND: HDL-associated paraoxonase (PON1) reduces oxidation of lipids in LDL, and activity is inversely related to coronary heart disease risk with a beneficial effect on the development of atherosclerosis. Risk factors associated with atherosclerosis, such as hypertension, dyslipidemia and smoking, also promote the progression of chronic glomerulonephritides which may therefore be associated with perturbations in PON1 activity. METHODS: We performed a genetic association study in patients with IgA nephropathy (IgAN) (n=115) compared with control subjects (n=118). The aim was to test whether polymorphisms in the PON1 coding region (Q192R and L55M) and its promoter (-108C/T and -162A/G) are associated with either IgAN or with the progression. We measured serum paraoxonase activity in 60 out of 115 patients. All patients had been followed up for more than 4 years. RESULTS: There were no differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M and -108C/T) between the patients and controls. However, the frequency distribution at -162 position (A/G) was significantly diffe-rent in IgAN (p=0.028, chi-square test) with a higher frequency of the heterozygote (0.017, Fisher exact test [FE]; odds ratio [OR] = 1.99; 95% confidence interval [95% CI], 1.14-3.47). Although there were no differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M and -162C/T) between the patients with progressive IgA and the nonprogressive patients, we found that the frequency of the C allele for the -108C/T polymorphism was elevated in those patients with nonprogressive disease (n=85) compared with those with progressive disease (n=30) (61% vs. 47%; p=0.070, FE; OR=1.75, 95% CI, 0.97-3.18). Furthermore, PON1 activity was significantly higher in nonprogressive patients compared with progressors (206 +/- 71 vs. 136 +/- 48; p<0.001), and activity significantly correlated with 1/serum creatinine (SCr) (p<0.001; r=0.38). CONCLUSIONS: The results of this study suggest that in IgAN, lower PON1 activity may be associated with the deterioration of kidney function. This could be due to variable expression of the PON1 gene, or a functional effect of the gene product.

Adult↗
PubMed1988

Definition of genetic factors in hypertension: a search for major genes, polygenes, and homogeneous subtypes.

Essential hypertension is a heterogeneous group of disorders with different causes. This report reviews approaches taken and results found in current studies of the genetic and environmental determinants of essential hypertension. Recent observations from the University of Utah Cardiovascular Genetics Research Clinic and published data from other studies are cited. Several biochemical tests show strong associations with hypertension and substantial major gene and/or polygenic determination including: urinary kallikrein excretion, intracellular sodium concentration, sodium-lithium countertransport, plasma haptoglobin phenotypes, MN blood groups, and familial dyslipidemia.

Genes↗
PubMed2001

[Polish Multicenter Study on Diabetes Epidemiology (PMSDE)--1998-2000].

Diabetes mellitus is a growing health problem at all ages in all countries. The Saint Vincent Declaration signed by the representatives of all European countries--among them by Poland--indicated the main goals to reduce this burden. This may be achieved by elaboration and initiation of the nation-wide programme for early detection and control of diabetes on the population level. The Polish Task Force for Diabetes Management worked out and put into operation in 1998 the project commissioned by the Ministry of Health funded by the Polish State Committee for Research (PBZ-018-11). The urgent need for the implementation of this programme was a result of the increasing number of diabetic patients on the primary health care level, diabetic complications and hospitalisations. The programme was based on the assumption that primary and secondary prevention of NIDDM may eliminate or reduce its risk factors and therefore decrease its prevalence and morbidity and should integrate epidemiology, identification of risk factors, education, intervention models and economics of diabetes. This issue of the Polish Archives of Internal Medicine contains the main results of the programme and reflects an actual situation of diabetes in Poland creating a rational basis for intervention on the population level. Evaluation of the incidence rate of the diabetes type 1 in 10 selected areas (population basis 30% of age group 0-29) revealed values from 8.4 to 14.7/100,000 in the age group 1-14 and from 4.4 to 11.2/100,000 in the age group 15-29. It accounts for the 2-3 fold increase in comparison with the results achieved in 1986 (Z. Szybinski). However an ascertainment of the register in the age group 15-29 dropped down during the last 10 years and additional sources of data must be involved in the survey. Prevalence of diabetes type 2 in 3 selected areas Krakow 10.77% (M. Szurkowska), Lublin 15.6% (J. Łopatynski) and Łódź 15.7% (J. Drzewoski) based on the population random sample over 35 years of age, constitutes over 90% of all patients with diabetes. When standardized to the Polish population the prevalence of diabetes type 2 accounts for 5.37% and reflects a true endemic state. With comparison to a similar survey carried out in 1986 in Wrocław the prevalence 3.71% of the diabetes type 2 increased 2-3 times. It allowed to calculate an actual number of patients with diabetes type 2--over 2 million and around 50% of them represents "unknown" diabetes. Such high contribution of the unknown non-diagnosed diabetes has been confirmed in the survey carried out in Poznań on the non-randomized professional group of persons (B. Wierusz-Wysocka) in investigation on the first-degree relatives of patients with known diabetes in Warsaw (T. Kasperska-Czyzyk) and in Wroclaw (R. Wasikowa). This raises the question about the criteria of diagnosis for unknown diabetes. Comparative analysis carried out in Krakow revealed that fasting glycemia 7.0 mmol/L allowed to diagnose diabetes with 50% with respect to the 2 hours oral glucose tolerance test (WHO 1985) and shouldn't be use as a tool for early diagnosis of diabetes type 2 (Z. Szybinski, M. Szurkowska) Identification of the risk factors in PMSDE for diabetes type 2 allowed to introduce the term "global risk factors", divided into two groups primary (obesity, age, pregnancy and genetic background) and secondary (hyperinsulinemia, hyperglycemia, dyslipidemia and hypertension). In the multifactor analysis obesity and hyperinsulinemia are the strongest predictors and modifiable risk factors of the development of diabetes type 2 and late complications. Especially hyperinsulinemia as an independent secondary risk factor for hypertension, dyslipidemia--in consequences late diabetic complications and perhaps carcinogenesis may play an important role as a predictor of diabetes type 2 and biochemical marker of effectiveness of non-pharmacological and pharmacological approach in the global concept of diabetes type 2 treatment (Z. Szybinski). Analysis of the late complications of diabetes were focussed on visual disability and lower extremity amputation due to diabetic foot development. Analysis of prevalence (PR) of visual disability due to diabetes in Krakow (J. Pantoflinski) and Olsztyn (E. Bandurska-Stankiewicz) revealed similar values, in the both areas around 6% of general visual disability in population. Monitoring of the visual disability in diabetic patients seems to be a good indicator of the quality level of the diabetic care. Analysis of the lower extremity amputation carried out in Krakow district (A. Nazim) revealed that incidence rate of amputation in diabetics was 15 times higher than in non-diabetics and in 10.8% of cases amputation was performed in unknown diabetes type 2. The preventive measures and non-pharmacological and pharmacological management approximately in diabetes should be solved with education based on the separate post of a diabetic educator within a diabetic team and on the primary health care level. The articles presenting elaborated educational model in diabetes are published in "Diabetologia Polska" (A. Czyzyk). Intervention model was tested in Krakow in the groups of obese patients with newly diagnosed "unknown" diabetes and was based on the 12 weeks supervised dietician education with standardized physical activity programme. In obese diabetic patients the weight loss less than 10% of the initial body weight can markedly improve biochemical parameters like hyperglycemia dyslipidemia and hyperinsulinemia without pharmacological therapy and 45% of patients has been transferred to the group of Impaired Glucose Tolerance (A. Gilis-Januszewska). Another model of intervention may be applied in menopausal women (J. Nadel, K. Cypryk) treated with hormonal replacement therapy as a complementary factor to education and if necessary to anti-diabetic drugs. Increase number of diabetic patients especially of the "unknown" type 2 has serious economic aspect by increasing a burden of patients, theirs families, society and health care system. Within PMSDE programme elaboration of the model for calculation the direct costs about of diabetes and burden in terms of years of life lost using DALY measure was performed (K. Kissimova-Skarbek). Average diabetes type 1 patients costs 7 times and type 2 over 3 times higher than average health care cost and 95% of total time lost due to disability is caused by diabetes type 2. Therefor primary and secondary prevention of diabetes typ 2 have highest priority among strategic preventive targets. The Review Conference held in Warsaw at 24-25 February 2001 in the presence of WHO Experts formulated the recommendations focused on: 1. Elaboration of high risk strategy for early diagnosis of unknown diabetes type 2 based on the 2-hours OGTT (WHO 1985) 2. Continuation of the epidemiologic study in diabetes 3. Instituting the professional post for diabetes educator on the specialized and primary health care levels. 4. Further research are recommended for evaluation of the role of fasting glycemia and hyperinsulinemia as predictors and risk factors of diabetes type 2, for development of preventive models in diabetes type 2 and for development of the economical models to asses the costs of diabetes (Recommendations).

Adult↗
PubMed1990

DNA based diagnostic tests: recombinant DNA and cardiovascular disease risk factors.

Advances in molecular biology and medical biotechnology are continuously creating exciting possibilities for DNA based diagnostics. It is now possible by simple procedures to detect polymorphic DNA markers, structural variants and regulatory mutants of human genes, allowing detailed genotyping of patients. The innovative combination of immunoenzymatic techniques, monoclonal antibodies and recombinant tracer proteins, results in new DNA based tests for the determination of important biochemical parameters, in order to define more precisely the phenotype and hence assess the individual risk. The application of these technologies to the analysis of dyslipidemias, atherosclerosis and cardiovascular diseases may not only lead to a better understanding of the molecular and genetic basis of these pathologies, but also to their early recognition and better management.

Base Sequence↗
PubMed1998

Did grandma give you heart disease? The new battle against coronary artery disease.

Atherosclerosis/coronary artery disease (CAD) is largely a result of genetically linked dyslipidemias that can often be identified in clinical practice. Expression of these genetic traits is highly individual and can be affected by environmental factors such as diet and exercise. By understanding the heterogeneity of CAD, it becomes clear that all patients cannot be optimally managed with the same therapeutic regimen. Whereas elevated low-density lipoprotein (LDL) cholesterol is strongly correlated with CAD risk, reduction of LDL cholesterol alone is not an adequate strategy in many cases. Patients with the small, dense LDL of the atherogenic lipoprotein profile (pattern B) experience a 3-fold increased risk of CAD, and pattern B is also correlated with the development of type 2 diabetes. Likewise, elevated lipoprotein(a) increases atherosclerotic risk, particularly in the presence of other risk factors, and is predictive of CAD risk in both women and men. Recent data show that the routine lipid profile--total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol--does not detect the most common inherited dyslipidemias. Newer, more sophisticated tests, such as gradient gel electrophoresis, can detect disease-relevant lipidemic details, e.g., LDL subclass pattern, LDL particle diameter, and LDL subregions. Although these testing procedures are more expensive, their cost must be weighed against the potential lifelong cost of sometimes expensive drug treatment that may be avoided based on the results of such tests. Thus, by attending to the implications of family history, the interactions of genetic, metabolic, and environmental factors, and utilizing more targeted testing procedures, physicians can match the patient's disorder with specifically effective therapy while maintaining a cost-effective approach to disease management.

Angioplasty, Balloon, Coronary↗
PubMed2006

In vivo role of the HNF4alpha AF-1 activation domain revealed by exon swapping.

The gene encoding the nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) generates isoforms HNF4alpha1 and HNF4alpha7 from usage of alternative promoters. In particular, HNF4alpha7 is expressed in the pancreas whereas HNF4alpha1 is found in liver, and mutations affecting HNF4alpha function cause impaired insulin secretion and/or hepatic defects in humans and in tissue-specific 'knockout' mice. HNF4alpha1 and alpha7 isoforms differ exclusively by amino acids encoded by the first exon which, in HNF4alpha1 but not in HNF4alpha7, includes the activating function (AF)-1 transactivation domain. To investigate the roles of HNF4alpha1 and HNF4alpha7 in vivo, we generated mice expressing only one isoform under control of both promoters, via reciprocal swapping of the isoform-specific first exons. Unlike Hnf4alpha gene disruption which causes embryonic lethality, these 'alpha7-only' and 'alpha1-only' mice are viable, indicating functional redundancy of the isoforms. However, the former show dyslipidemia and preliminary results indicate impaired glucose tolerance for the latter, revealing functional specificities of the isoforms. These 'knock-in' mice provide the first test in vivo of the HNF4alpha AF-1 function and have permitted identification of AF-1-dependent target genes.

Alternative Splicing↗