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Broadly, in hereditary diseases there may be two contributing factors:
Broadly, in hereditary diseases there may be two contributing factors:
#A certain defect in the sperm and ovum (referred to as ''bija dosha'') results in a genetic disorder or genetic predisposition to disease. Regarding ''prameha'', [[Charaka Samhita]] mentions that excessive indulgence in ''madhura rasa'' (foods/ drinks with a sweet taste) by the parents is the chief cause of this chromosomal damage to the sperm and ovum.
#A certain defect in the sperm and ovum (referred to as ''bija dosha'') results in a genetic disorder or genetic predisposition to disease. Regarding ''prameha'', [[Charak Samhita]] mentions that excessive indulgence in ''madhura rasa'' (foods/ drinks with a sweet taste) by the parents is the chief cause of this chromosomal damage to the sperm and ovum.
#An intrauterine environment that negatively affects the development of the fetus due to the mother’s diet, lifestyle, or adverse psychological state during pregnancy. This congenital aspect can trigger the disease process for which there is a genetic predisposition. Regarding ''prameha'', the overindulgence of ''madhura rasa'' by the mother during pregnancy is likely to trigger ''prameha''.
#An intrauterine environment that negatively affects the development of the fetus due to the mother’s diet, lifestyle, or adverse psychological state during pregnancy. This congenital aspect can trigger the disease process for which there is a genetic predisposition. Regarding ''prameha'', the overindulgence of ''madhura rasa'' by the mother during pregnancy is likely to trigger ''prameha''.
The diet, lifestyle, and adverse psychological state of the mother during lactation (and only during the stage of pregnancy)may also play a decisive role in precipitating ''prameha'' in the infants. In addition, excessive intake of ''madhura rasa'' during childhood can contribute to the onset of ''prameha'' in children who are genetically predisposed. Thus, hereditary predisposition and unwholesome dietary and lifestyle choices, especially excessive intake of ''madhura rasa'', can play a combined role to cause hereditary ''prameha''. The description of ''sahaja prameha'' in Sushruta Samhita and ''jatah prameha'' in [[Charaka Samhita]] are quite similar to that of type-I diabetes (also known as insulin- dependent diabetes mellitus or juvenile- onset diabetes). ''Jatah pramehi madhumehino'', as defined in [[Charaka Samhita]], correlates with type-I diabetes beginning in early childhood.
The diet, lifestyle, and adverse psychological state of the mother during lactation (and only during the stage of pregnancy)may also play a decisive role in precipitating ''prameha'' in the infants. In addition, excessive intake of ''madhura rasa'' during childhood can contribute to the onset of ''prameha'' in children who are genetically predisposed. Thus, hereditary predisposition and unwholesome dietary and lifestyle choices, especially excessive intake of ''madhura rasa'', can play a combined role to cause hereditary ''prameha''. The description of ''sahaja prameha'' in Sushruta Samhita and ''jatah prameha'' in [[Charak Samhita]] are quite similar to that of type-I diabetes (also known as insulin- dependent diabetes mellitus or juvenile- onset diabetes). ''Jatah pramehi madhumehino'', as defined in [[Charak Samhita]], correlates with type-I diabetes beginning in early childhood.
===== ''Apathyanimittaja prameha'' (acquired) =====
===== ''Apathyanimittaja prameha'' (acquired) =====
===== Classification by ''Dosha''/Stage of Progression =====
===== Classification by ''Dosha''/Stage of Progression =====
As for all other disease systems described in Ayurvedic texts, ''prameha'' has been classified according to the predominant ''dosha'' in the disease process. Ayurveda describes three distinct categories of ''prameha'' by ''dosha'', i.e., ''kaphaja, pittaja,'' and ''vataja prameha''<ref> Shastri KN, Chaturvedi GN. Agnivesha, Charaka Samhita, Vidyotini Commentary. Varanasi, India : Chaukhamba Bharti Academy, 2004. </ref> <ref> Shukla VD, Tripathi RD. Agnivesha, Charaka Samhita, Vaidyamanorama Hindi Commentary. Delhi, India; Chaukhamba Sanskrit Pratisthana, 2002. </ref>. However, it is important to note here that the dominance of a ''dosha'' varies as the disease progresses. In the initial stage, ''kapha'' is in excess, which vitiates ''meda'' and ''kleda'' causing ''kaphaja prameha''.
As for all other disease systems described in Ayurvedic texts, ''prameha'' has been classified according to the predominant ''dosha'' in the disease process. Ayurveda describes three distinct categories of ''prameha'' by ''dosha'', i.e., ''kaphaja, pittaja,'' and ''vataja prameha''<ref> Shastri KN, Chaturvedi GN. Agnivesha, Charak Samhita, Vidyotini Commentary. Varanasi, India : Chaukhamba Bharti Academy, 2004. </ref> <ref> Shukla VD, Tripathi RD. Agnivesha, Charak Samhita, Vaidyamanorama Hindi Commentary. Delhi, India; Chaukhamba Sanskrit Pratisthana, 2002. </ref>. However, it is important to note here that the dominance of a ''dosha'' varies as the disease progresses. In the initial stage, ''kapha'' is in excess, which vitiates ''meda'' and ''kleda'' causing ''kaphaja prameha''.
Further progression results in the loss (or ''kshaya'') of ''kapha''. ''Pitta'' then predominates, which vitiates the blood (''rakta''), precipitating ''pittaja prameha''. Further progression results in loss of ''pitta''. This leads to vitiation of ''vata'', which weans the body of vital substances/vital essence through urine, precipitating ''vataja prameha''<ref> Chandola HM, Bhatia S. Concept of Diabetes mellitus in Ayurveda and its treatment with certain indigenous drugs. AYU Int 2001;1:84-87. </ref>. Charaka says that any of these three types of ''prameha'' can be precipitated directly, depending upon genetic predisposition and improper diet and lifestyle.
Further progression results in the loss (or ''kshaya'') of ''kapha''. ''Pitta'' then predominates, which vitiates the blood (''rakta''), precipitating ''pittaja prameha''. Further progression results in loss of ''pitta''. This leads to vitiation of ''vata'', which weans the body of vital substances/vital essence through urine, precipitating ''vataja prameha''<ref> Chandola HM, Bhatia S. Concept of Diabetes mellitus in Ayurveda and its treatment with certain indigenous drugs. AYU Int 2001;1:84-87. </ref>. Charak says that any of these three types of ''prameha'' can be precipitated directly, depending upon genetic predisposition and improper diet and lifestyle.
Correlating the ''doshic'' classification of ''prameha'' with the etiology, ''kaphaja'' and ''pittaja prameha'' are always ''apathyanimittaja'' ''prameha'' (acquired), while ''vataja prameha'' can be hereditary or acquired. If ''kaphaja'' and ''pittaja'' ''prameha'' are not managed properly, in due course of time they lead to ''madhumeha'' (a subtype of ''vataja prameha''), which is a terminal stage of the disease and is said to be incurable<ref> Tripathi SN, Chandola HM.Study on variations in diabetes mellitus (Prameha) with special reference to plasma insulin, cortisol and catecholamines. In Bajaj JS,ed. Diabetes mellitus in Developing Countries. New Delhi, India: Interprint, 1984:125-128. </ref>. This disease can be equated with the terminal stage of type 2 diabetes, which progresses to insulin- dependent diabetes. It has been observed that in the ''pittaja'' stage of ''prameha'', there is a tendency toward moderate hyperglycemia, which may be due to increased adrenal medullary and cortical activities. In ''vataja prameha'', there may be severe hyperglycemia with hypoinsulinemia.<ref> Sharma H, Chandola HM..Prameha in Ayurveda: Correlation with Obesity, Metabolic Syndrome, and Diabetes Mellitus.Part 1-Etiology, Classification, and Pathogenesis. The Journal of Alternative and Complementary Medicine.2011. 17(6):491-496. </ref>
Correlating the ''doshic'' classification of ''prameha'' with the etiology, ''kaphaja'' and ''pittaja prameha'' are always ''apathyanimittaja'' ''prameha'' (acquired), while ''vataja prameha'' can be hereditary or acquired. If ''kaphaja'' and ''pittaja'' ''prameha'' are not managed properly, in due course of time they lead to ''madhumeha'' (a subtype of ''vataja prameha''), which is a terminal stage of the disease and is said to be incurable<ref> Tripathi SN, Chandola HM.Study on variations in diabetes mellitus (Prameha) with special reference to plasma insulin, cortisol and catecholamines. In Bajaj JS,ed. Diabetes mellitus in Developing Countries. New Delhi, India: Interprint, 1984:125-128. </ref>. This disease can be equated with the terminal stage of type 2 diabetes, which progresses to insulin- dependent diabetes. It has been observed that in the ''pittaja'' stage of ''prameha'', there is a tendency toward moderate hyperglycemia, which may be due to increased adrenal medullary and cortical activities. In ''vataja prameha'', there may be severe hyperglycemia with hypoinsulinemia.<ref> Sharma H, Chandola HM..Prameha in Ayurveda: Correlation with Obesity, Metabolic Syndrome, and Diabetes Mellitus.Part 1-Etiology, Classification, and Pathogenesis. The Journal of Alternative and Complementary Medicine.2011. 17(6):491-496. </ref>
As mentioned earlier, ''prameha'' can be correlated with obesity, metabolic syndrome, and diabetes mellitus. The early manifestation of the disease process in these conditions is characterized by lipid, carbohydrate, and protein metabolism disturbances accompanied by glycosuria, proteinuria, etc., which can be equates with a ''kaphaja'' condition (i.e., which can be easily controlled and cured. ''Pittaja prameha'' can be correlated with the inflammatory conditions accompanied with diabetes like urinary tract infection and diabetic ketoacidosis. The advanced stage of disease, with metabolic disturbances associated with loss of immunity, correlates with type 2 diabetes that has progressed to insulin dependent diabetes, and correlates with the hereditary form of type 1 diabetes, which both correlate with ''vataja prameha''. Both of these forms are incurable as described by Charaka.
As mentioned earlier, ''prameha'' can be correlated with obesity, metabolic syndrome, and diabetes mellitus. The early manifestation of the disease process in these conditions is characterized by lipid, carbohydrate, and protein metabolism disturbances accompanied by glycosuria, proteinuria, etc., which can be equates with a ''kaphaja'' condition (i.e., which can be easily controlled and cured. ''Pittaja prameha'' can be correlated with the inflammatory conditions accompanied with diabetes like urinary tract infection and diabetic ketoacidosis. The advanced stage of disease, with metabolic disturbances associated with loss of immunity, correlates with type 2 diabetes that has progressed to insulin dependent diabetes, and correlates with the hereditary form of type 1 diabetes, which both correlate with ''vataja prameha''. Both of these forms are incurable as described by Charak.
==== ''Prameha'' classified according to physique ====
==== ''Prameha'' classified according to physique ====
[[Charaka Samhita]] has classified the patients of ''prameha'' into two main categories on the basis of their body constitution with regard to physique::
[[Charak Samhita]] has classified the patients of ''prameha'' into two main categories on the basis of their body constitution with regard to physique::
#''Sthula pramehi'' refers to obese diabetic patients and corresponds to individuals with Type 2 diabetes, and
#''Sthula pramehi'' refers to obese diabetic patients and corresponds to individuals with Type 2 diabetes, and
===== ''Mamsadhatu'' =====
===== ''Mamsadhatu'' =====
It is one of the main ''dushyas'' (vitiating factors) described by Charaka in regards to ''prameha''. He narrated it especially in ''kaphaja prameha'' and ''avaranjanya madhumeha''. ''Mamsa'' and ''Kapha'' possess similar qualities and both give strength to the body. When vitiated, ''mamsa'' loses its normal consistency and develops ''shaithilya'' and provide space in between for the accumulation of morbid matter. That in turn results in ''putimamsa pidika'' (Ca.Ni. 4/8). ''Mamsa dushti'' can be compared to deranged protein metabolism which is an integral part of diabetes mellitus. Research studies have found that glucocorticoid activities and acidosis stimulates protein and amino acid catabolism <ref> May, RC et al. 1996. Glucocorticoids and acidosis stimulate protein and amino acid catabolism in vivo. Kidney Int. 1996 Mar;49(3):679-83. </ref>. Amino acids breakdown in liver results in increased production of urea<ref> Vaudevan et al. 2011. Textbook of biochemistry for medical students, Sixth Edition, JP Medical Publishers </ref> and these free amino acids can be compared with ''abaddha mamsa''. ''Putimamsa'' and ''pidaka'' are the morbid states of ''mamsa dhatu''. Two major changes take place in ''mamsa dhatu'' - protein degradation and reduction in its blood supply, both of which along with elevated blood sugar level form a favorable media for the growth and multiplication of microorganisms. The results are putrefaction and evolution of multiple septic foci in ''mamsa dhatu''. Diminished protein synthesis hampers the healing process and these complications adopt chronic course.
It is one of the main ''dushyas'' (vitiating factors) described by Charak in regards to ''prameha''. He narrated it especially in ''kaphaja prameha'' and ''avaranjanya madhumeha''. ''Mamsa'' and ''Kapha'' possess similar qualities and both give strength to the body. When vitiated, ''mamsa'' loses its normal consistency and develops ''shaithilya'' and provide space in between for the accumulation of morbid matter. That in turn results in ''putimamsa pidika'' (Ca.Ni. 4/8). ''Mamsa dushti'' can be compared to deranged protein metabolism which is an integral part of diabetes mellitus. Research studies have found that glucocorticoid activities and acidosis stimulates protein and amino acid catabolism <ref> May, RC et al. 1996. Glucocorticoids and acidosis stimulate protein and amino acid catabolism in vivo. Kidney Int. 1996 Mar;49(3):679-83. </ref>. Amino acids breakdown in liver results in increased production of urea<ref> Vaudevan et al. 2011. Textbook of biochemistry for medical students, Sixth Edition, JP Medical Publishers </ref> and these free amino acids can be compared with ''abaddha mamsa''. ''Putimamsa'' and ''pidaka'' are the morbid states of ''mamsa dhatu''. Two major changes take place in ''mamsa dhatu'' - protein degradation and reduction in its blood supply, both of which along with elevated blood sugar level form a favorable media for the growth and multiplication of microorganisms. The results are putrefaction and evolution of multiple septic foci in ''mamsa dhatu''. Diminished protein synthesis hampers the healing process and these complications adopt chronic course.
===== ''Majjadhatu'' =====
===== ''Majjadhatu'' =====
===== ''Vasa'' =====
===== ''Vasa'' =====
Charak described it as a subtype of ''vatajaprameha'' i.e. ''vasameha''. ''Vasa'' is the ''upadhatu'' (minor tissue or sub-tissue) of ''mamsa'' and the unctuousness present in the ''mamsa dhatu'' is called ''vasa''.
===== ''Lasika'' =====
===== ''Lasika'' =====
The pathogenesis of ''vataja prameha'' is similar to that of type-1 diabetes mellitus. ''Vata'' is agitated due to various precipitating causes acts on the body in such a way that there is passage of ''vasa'' (fat), ''majja'' (bone marrow), ''lasika'' (lymph), and ''ojas'' (essence of the body /immune substances / vitality) through the urine. This condition indicates impaired renal function as a result of diabetes, leading to a dire prognosis. Due to ''dhatukshaya'' (loss of body tissues) the patient become very weak and emaciated.
The pathogenesis of ''vataja prameha'' is similar to that of type-1 diabetes mellitus. ''Vata'' is agitated due to various precipitating causes acts on the body in such a way that there is passage of ''vasa'' (fat), ''majja'' (bone marrow), ''lasika'' (lymph), and ''ojas'' (essence of the body /immune substances / vitality) through the urine. This condition indicates impaired renal function as a result of diabetes, leading to a dire prognosis. Due to ''dhatukshaya'' (loss of body tissues) the patient become very weak and emaciated.
[[Charaka Samhita]] deals with very specific pathogenesis for ''madhumeha'', which is a subtype of ''vataja prameha''. When an individual excessively consumes the foods that cause ''prameha, kapha'' and ''pitta'' become vitiated, then adipose tissues and muscle tissuses become disturbed and causes impaired functioning of ''vata''. Subsequently ''vata'' gets vitiated and extends to urinary bladder along with ''ojas'', resulting in ''ojas'' being expelled in the urine. In Ayurveda, ''ojas'' is considered vital to the maintanence of health; its loss in ''prameha'' leads to many complications, including ''prameha pidika'' (boils and carbuncles). This advanced condition is comparable to non-insulin –dependent type -2 diabetes progressing into insulin dependent diabetes. It is the stage of diabetes in which there are complications, including nephropathy, which result in vital substances of the body being excreted through urine.
[[Charak Samhita]] deals with very specific pathogenesis for ''madhumeha'', which is a subtype of ''vataja prameha''. When an individual excessively consumes the foods that cause ''prameha, kapha'' and ''pitta'' become vitiated, then adipose tissues and muscle tissuses become disturbed and causes impaired functioning of ''vata''. Subsequently ''vata'' gets vitiated and extends to urinary bladder along with ''ojas'', resulting in ''ojas'' being expelled in the urine. In Ayurveda, ''ojas'' is considered vital to the maintanence of health; its loss in ''prameha'' leads to many complications, including ''prameha pidika'' (boils and carbuncles). This advanced condition is comparable to non-insulin –dependent type -2 diabetes progressing into insulin dependent diabetes. It is the stage of diabetes in which there are complications, including nephropathy, which result in vital substances of the body being excreted through urine.
Among patients with significant proteinuria, the degeneration of cells within epithelial casts may result in a characteristic "Maltese Cross" appearance and a fatty cast. These droplets are composed of cholesterol esters and cholesterol, which may also be observed free in the urine. This may be correlated with ''vasameha'' (lipiduria). ''Majjameha'' can be correlated with appearance of waxy casts in urine in advanced renal failure. Waxy cast are thought to be the last stage of the degeneration of a granular cast. Since this degenerative process is probably slow, it is most likely observed in nephrons with much diminished flow. Waxy casts are therefore most consistent with the presence of advanced renal failure.<ref> https://www.slideshare.net/sprince33/glomerulonephritis accessed on 12 June 2017 </ref>
Among patients with significant proteinuria, the degeneration of cells within epithelial casts may result in a characteristic "Maltese Cross" appearance and a fatty cast. These droplets are composed of cholesterol esters and cholesterol, which may also be observed free in the urine. This may be correlated with ''vasameha'' (lipiduria). ''Majjameha'' can be correlated with appearance of waxy casts in urine in advanced renal failure. Waxy cast are thought to be the last stage of the degeneration of a granular cast. Since this degenerative process is probably slow, it is most likely observed in nephrons with much diminished flow. Waxy casts are therefore most consistent with the presence of advanced renal failure.<ref> https://www.slideshare.net/sprince33/glomerulonephritis accessed on 12 June 2017 </ref>
A burning sensation in the hands and feet is an important feature of neuropathy that results from diabetes mellitus. Excessive sweat as a consequence of obesity may result in bacterial growth that leads to body odor. Excessive thirst may be directly related to disturbed glucose metabolism. Thus, the symptoms described in the ''poorvarupa'' of ''prameha'' include prediabetic symptoms and the early manifestation (vascular changes, obesity, etc.) of diabetes or subclinical diabetes.
A burning sensation in the hands and feet is an important feature of neuropathy that results from diabetes mellitus. Excessive sweat as a consequence of obesity may result in bacterial growth that leads to body odor. Excessive thirst may be directly related to disturbed glucose metabolism. Thus, the symptoms described in the ''poorvarupa'' of ''prameha'' include prediabetic symptoms and the early manifestation (vascular changes, obesity, etc.) of diabetes or subclinical diabetes.
The role of ''meda'' (fat/adipose tissues) is of great importance in the pathogenesis of ''prameha''. Its role is not as ''dushya'' (disturbed functioning of the ''dhatus''), but something more than that. According to [[Charaka Samhita]], ''bahudrava shleshma'' (kapha that contains too much liquid) joins and affects ''meda'', causing it to become ''abaddha'' (unobstructed or fluid) in Ayurveda. This has been described as ''sharira-kleda'' (body of fluid) in Ayurveda. Thus, excess water in the blood causes increased diuresis. It is very important to elaborate the term ''bahudrava shlesma''. ''Shleshma/ kapha'' is one among the three basic humors regulating all physiological and psychological process in the living organism. At its normal state, it causes binding of body tissues i.e. maintain the tissues integrity, represent the normal cell mediated immunity etc. ''Bahudrava'' means that ''kapha'' loses its natural properties and get vitiated, it is important to mention here that this derangement may be acquired or congenital, Whatever may be the cause this vitiated ''kapha'', it is unable to perform its normal functions. Describing the physical properties of ''kapha'' it is mentioned that it is unctuous in touch and looks like ''ghrita'' (ghee). Thus, it can be said that ''kapha'' in body represents lipid components of the body and vitiated ''kapha'' can be correlated with dyslipidemia. Role of dyslipidemia and metabolic abnormalities in the pathogenesis of diabetes is very obvious and well elaborated in modern medicine. Among the metabolic abnormalities that commonly accompany diabetes are disturbances in the production and clearance of plasma lipoproteins. Moreover, development of dyslipidemia may be a harbinger of future diabetes. A characteristic pattern, termed diabetic dyslipidemia, consists of low high density lipoprotein (HDL), increased triglycerides, and postprandial lipemia. This pattern is most frequently seen in type 2 diabetes and may be a treatable risk factor for subsequent cardiovascular disease.<ref> http://press.endocrine.org/doi/10.1210/jcem.86.3.7304 accessed on 12 June 2017 </ref>
The role of ''meda'' (fat/adipose tissues) is of great importance in the pathogenesis of ''prameha''. Its role is not as ''dushya'' (disturbed functioning of the ''dhatus''), but something more than that. According to [[Charak Samhita]], ''bahudrava shleshma'' (kapha that contains too much liquid) joins and affects ''meda'', causing it to become ''abaddha'' (unobstructed or fluid) in Ayurveda. This has been described as ''sharira-kleda'' (body of fluid) in Ayurveda. Thus, excess water in the blood causes increased diuresis. It is very important to elaborate the term ''bahudrava shlesma''. ''Shleshma/ kapha'' is one among the three basic humors regulating all physiological and psychological process in the living organism. At its normal state, it causes binding of body tissues i.e. maintain the tissues integrity, represent the normal cell mediated immunity etc. ''Bahudrava'' means that ''kapha'' loses its natural properties and get vitiated, it is important to mention here that this derangement may be acquired or congenital, Whatever may be the cause this vitiated ''kapha'', it is unable to perform its normal functions. Describing the physical properties of ''kapha'' it is mentioned that it is unctuous in touch and looks like ''ghrita'' (ghee). Thus, it can be said that ''kapha'' in body represents lipid components of the body and vitiated ''kapha'' can be correlated with dyslipidemia. Role of dyslipidemia and metabolic abnormalities in the pathogenesis of diabetes is very obvious and well elaborated in modern medicine. Among the metabolic abnormalities that commonly accompany diabetes are disturbances in the production and clearance of plasma lipoproteins. Moreover, development of dyslipidemia may be a harbinger of future diabetes. A characteristic pattern, termed diabetic dyslipidemia, consists of low high density lipoprotein (HDL), increased triglycerides, and postprandial lipemia. This pattern is most frequently seen in type 2 diabetes and may be a treatable risk factor for subsequent cardiovascular disease.<ref> http://press.endocrine.org/doi/10.1210/jcem.86.3.7304 accessed on 12 June 2017 </ref>
==== Causes of lipoprotein abnormalities in diabetes <ref> Goldberg J.Ira . Diabetic Dyslipidemia: Causes and Consequences .The Journal of Clinical Endocrinology & Metabolism. 2001. 86 (3): 965-971. </ref>====
==== Causes of lipoprotein abnormalities in diabetes <ref> Goldberg J.Ira . Diabetic Dyslipidemia: Causes and Consequences .The Journal of Clinical Endocrinology & Metabolism. 2001. 86 (3): 965-971. </ref>====