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Is maturity onset diabetes at young age (MODY) more common in Europe than previously assumed?
studies showed normalisation of all
previous abnormalities
of
neighbouring areas of Germany seems unlikely, MODY quite so rare as previously estimated. These data are not only important for epidemiologists but also for patients who may seek medical advice concerning family planning, a very relevant issue in a highly hereditary may not be
(table). This
patient’s history, physical examination, clinical strongly suggested RMSF and his IFA titre satisfied laboratory criteria for the diagnosis.2 Although unusual, urban foci of RMSF have been reported. New York city’s first cases were documented in 1987.3 Since then, 24 cases have been reported to the New York City Department of Health; 18 (75%) without recent travel outside the city. Soundview Park in the course, and response to treatment
Bronx, where D variabilis ticks infected with R rickettsii have been found,3 was the unlikely source of exposure for most. Central Park is routinely dragged for ticks and although D variabilis are regularly found, none has been infected with R rickettsii. This case is also unusual for the absolute lymphopenia, including CD4 cell RMSF is lymphocytopenia. Although commonly associated with thrombocytopenia and anaemia, typically the leucocyte count is normal but often with an increased percent of immature forms." Our patient’s severe absolute lymphopenia and CD4 cell lymphocytopenia returned to normal after treatment and resolution of his illness. RMSF should be added to the list of conditions that can be associated with reversible total CD4 and in with a clinical lymphocytopenia. Also, patients suggestive presentation, lack of an exposure to a known focus on RMSF should not rule out the diagnosis.
disease. We also found that MODY patients had had a much poorer diabetes education than patients with IDDM, whose more dramatic onset of diabetes mostly also occurs at young age. Only 10-5% MODY diabetics were adequately trained between 1986 and 1989 compared with 27-6% IDDM patients. During the past 4 years these figures have risen to 57-7% for IDDM but only 26-3% for MODY. Since education is widely accepted to be the basis of diabetes treatment, this moderate improvement cannot be regarded as sufficient. We conclude that MODY is much more common in central Europe than previously assumed and should be better known, understood, and treated. Hellmuth M Ledermann Eleonoren-Klinik, D-64678 Lindenfels-Winterkasten, Germany
1
2
Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile onset type diabetes in young people. Diabetes 1975; 24: 44-53. Panzram G, Adolph W. Heterogeneity of maturity onset diabetes at young age (MODY). Lancet 1981; ii: 986.
*Glenn S Turett, Edward E Telzak, James Crooks, Barkat A Fazal *Division of Infectious Diseases, Bronx-Lebanon Hospital Center, Bronx, NY 10457, USA; and Samaritan Village, Bronx
1 2
Rocky Mountain spotted fever—United States, 1990. MMWR Morb Mortal Wkly Rep 1991; 40: 451-59. Case definitions for public health surveillance-recommendations and reports. MMWR Morb Mortal Wkly Rep 1990; 39 (RR13): 30-31.
3
4
Salgo MP, Telzak EE, Currie B. A focus of Rocky Mountain spotted fever within New York City. N Engl J Med 1988; 318: 1345-48. Weber DJ, Walker DH. Rocky Mountain spotted fever. North Am 1991; 5: 19-35.
Infect Dis Clin
Is
maturity onset diabetes at young age (MODY) more common in Europe than previously assumed? SIR-From 1986-94 we screened 2064 diabetics (1798 noninsulin-dependent diabetes mellitus [NIDDM], 266 insulindependent diabetes mellitus [IDDM]) in the German district of Hesse. In this group we found 38 patients (22 male, 16 female) fulfilling the maturity onset diabetes at young age (MODY) criteria of Tattersall and Fajans’ (diagnosis before the age of 25 years and treated successfully with diet or oral drugs for 5 years). All these patients had at least one first-degree relative with diabetes mellitus. MODY is now of particular interest because the illness may serve a as genetic model for NIDDM, one of the major metabolic disorders throughout the world with a fast rising incidence. In 1981 Panzram and Adolph2 published results of a survey of 40927 East German diabetics of whom they collected a subgroup of 58 MODY patients (0-14%). According to our results MODY seems to be 12-9 times more frequent (1-8% of all diabetics) and as much as 15 times more frequent with regard to the NIDDM group (2-1%). Since such a vast difference in epidemiological data 648
Tumour necrosis factor SIR-Tracey’s commentary (Jan 14, p 75), we believe, is also relevant to pre-eclamptic toxaemia (PET). Many features of PET could be explained’ if tumour necrosis factor (TNF) is taken as the prime mediator: this implies chronic excessive free radical production, stimulated lipid metabolism, and increased lipid peroxidation, leading to adverse effects on conceptus and mother. The two-edged potential of the cytokine is central to the disease-it is both growth stimulating and, by its pro-oxidant effect, cytotoxic. Once antioxidant homoeostasis is overwhelmed, a vicious cytotoxic circle could be set up by oxidation of the inhibitor of the TNF promoter nuclear factor kappa B.2 Our evidence for the participation of TNF in PET is based particularly on changes in the blood concentration of a related protein, soluble TNF receptor I (sTNF.RI). In an ethically approved project, samples of blood were taken from women either routinely attending antenatally or admitted with proteinuric pre-eclampsia (two had thrombocytopenia). Serum and edetic acid (EDTA) plasma were separated within 2 h of withdrawal and kept as 500 µL samples at - 70° until assayed. The concentrations of TNF, sTNF.RI, and sTNF.RII were measured in ELISA plates (R and D systems, Minneapolis, USA). High sensitivity plates were used for the TNF assays in the range 0-32 pg/mL. TNF values (table) were heavily skewed: a comparison of the medians between the two groups showed no significant difference (p=0-18). Analysis of variance of sTNF.RI values shows that the values from the PET patients are significantly greater (p=0005) than those from normal pregnancies. sTNF.RI might be a more lasting index of TNF perturbation, because of a longer half-life in the bloodstream. The values for sTNF.RII in normal and preeclamptic pregnancies did not differ significantly (data not
shown). Austgulen and colleagues3 suggested a protective role for this protein. However it may potentiate’ both TNF-induced growth promotion and cytotoxicity. Significant increases in
previous abnormalities
of
neighbouring areas of Germany seems unlikely, MODY quite so rare as previously estimated. These data are not only important for epidemiologists but also for patients who may seek medical advice concerning family planning, a very relevant issue in a highly hereditary may not be
(table). This
patient’s history, physical examination, clinical strongly suggested RMSF and his IFA titre satisfied laboratory criteria for the diagnosis.2 Although unusual, urban foci of RMSF have been reported. New York city’s first cases were documented in 1987.3 Since then, 24 cases have been reported to the New York City Department of Health; 18 (75%) without recent travel outside the city. Soundview Park in the course, and response to treatment
Bronx, where D variabilis ticks infected with R rickettsii have been found,3 was the unlikely source of exposure for most. Central Park is routinely dragged for ticks and although D variabilis are regularly found, none has been infected with R rickettsii. This case is also unusual for the absolute lymphopenia, including CD4 cell RMSF is lymphocytopenia. Although commonly associated with thrombocytopenia and anaemia, typically the leucocyte count is normal but often with an increased percent of immature forms." Our patient’s severe absolute lymphopenia and CD4 cell lymphocytopenia returned to normal after treatment and resolution of his illness. RMSF should be added to the list of conditions that can be associated with reversible total CD4 and in with a clinical lymphocytopenia. Also, patients suggestive presentation, lack of an exposure to a known focus on RMSF should not rule out the diagnosis.
disease. We also found that MODY patients had had a much poorer diabetes education than patients with IDDM, whose more dramatic onset of diabetes mostly also occurs at young age. Only 10-5% MODY diabetics were adequately trained between 1986 and 1989 compared with 27-6% IDDM patients. During the past 4 years these figures have risen to 57-7% for IDDM but only 26-3% for MODY. Since education is widely accepted to be the basis of diabetes treatment, this moderate improvement cannot be regarded as sufficient. We conclude that MODY is much more common in central Europe than previously assumed and should be better known, understood, and treated. Hellmuth M Ledermann Eleonoren-Klinik, D-64678 Lindenfels-Winterkasten, Germany
1
2
Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile onset type diabetes in young people. Diabetes 1975; 24: 44-53. Panzram G, Adolph W. Heterogeneity of maturity onset diabetes at young age (MODY). Lancet 1981; ii: 986.
*Glenn S Turett, Edward E Telzak, James Crooks, Barkat A Fazal *Division of Infectious Diseases, Bronx-Lebanon Hospital Center, Bronx, NY 10457, USA; and Samaritan Village, Bronx
1 2
Rocky Mountain spotted fever—United States, 1990. MMWR Morb Mortal Wkly Rep 1991; 40: 451-59. Case definitions for public health surveillance-recommendations and reports. MMWR Morb Mortal Wkly Rep 1990; 39 (RR13): 30-31.
3
4
Salgo MP, Telzak EE, Currie B. A focus of Rocky Mountain spotted fever within New York City. N Engl J Med 1988; 318: 1345-48. Weber DJ, Walker DH. Rocky Mountain spotted fever. North Am 1991; 5: 19-35.
Infect Dis Clin
Is
maturity onset diabetes at young age (MODY) more common in Europe than previously assumed? SIR-From 1986-94 we screened 2064 diabetics (1798 noninsulin-dependent diabetes mellitus [NIDDM], 266 insulindependent diabetes mellitus [IDDM]) in the German district of Hesse. In this group we found 38 patients (22 male, 16 female) fulfilling the maturity onset diabetes at young age (MODY) criteria of Tattersall and Fajans’ (diagnosis before the age of 25 years and treated successfully with diet or oral drugs for 5 years). All these patients had at least one first-degree relative with diabetes mellitus. MODY is now of particular interest because the illness may serve a as genetic model for NIDDM, one of the major metabolic disorders throughout the world with a fast rising incidence. In 1981 Panzram and Adolph2 published results of a survey of 40927 East German diabetics of whom they collected a subgroup of 58 MODY patients (0-14%). According to our results MODY seems to be 12-9 times more frequent (1-8% of all diabetics) and as much as 15 times more frequent with regard to the NIDDM group (2-1%). Since such a vast difference in epidemiological data 648
Tumour necrosis factor SIR-Tracey’s commentary (Jan 14, p 75), we believe, is also relevant to pre-eclamptic toxaemia (PET). Many features of PET could be explained’ if tumour necrosis factor (TNF) is taken as the prime mediator: this implies chronic excessive free radical production, stimulated lipid metabolism, and increased lipid peroxidation, leading to adverse effects on conceptus and mother. The two-edged potential of the cytokine is central to the disease-it is both growth stimulating and, by its pro-oxidant effect, cytotoxic. Once antioxidant homoeostasis is overwhelmed, a vicious cytotoxic circle could be set up by oxidation of the inhibitor of the TNF promoter nuclear factor kappa B.2 Our evidence for the participation of TNF in PET is based particularly on changes in the blood concentration of a related protein, soluble TNF receptor I (sTNF.RI). In an ethically approved project, samples of blood were taken from women either routinely attending antenatally or admitted with proteinuric pre-eclampsia (two had thrombocytopenia). Serum and edetic acid (EDTA) plasma were separated within 2 h of withdrawal and kept as 500 µL samples at - 70° until assayed. The concentrations of TNF, sTNF.RI, and sTNF.RII were measured in ELISA plates (R and D systems, Minneapolis, USA). High sensitivity plates were used for the TNF assays in the range 0-32 pg/mL. TNF values (table) were heavily skewed: a comparison of the medians between the two groups showed no significant difference (p=0-18). Analysis of variance of sTNF.RI values shows that the values from the PET patients are significantly greater (p=0005) than those from normal pregnancies. sTNF.RI might be a more lasting index of TNF perturbation, because of a longer half-life in the bloodstream. The values for sTNF.RII in normal and preeclamptic pregnancies did not differ significantly (data not
shown). Austgulen and colleagues3 suggested a protective role for this protein. However it may potentiate’ both TNF-induced growth promotion and cytotoxicity. Significant increases in